Displaying publications 1 - 20 of 24 in total

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  1. Genetic variation at the Th2 immune gene IL13 is associated with IgE-mediated paediatric food allergy
    Ashley SE, Tan HT, Peters R, Allen KJ, Vuillermin P, Dharmage SC, et al.
    Clin Exp Allergy, 2017 Aug;47(8):1032-1037.
    PMID: 28544327 DOI: 10.1111/cea.12942
    BACKGROUND: Food allergies pose a considerable world-wide public health burden with incidence as high as one in ten in 12-month-old infants. Few food allergy genetic risk variants have yet been identified. The Th2 immune gene IL13 is a highly plausible genetic candidate as it is central to the initiation of IgE class switching in B cells.

    OBJECTIVE: Here, we sought to investigate whether genetic polymorphisms at IL13 are associated with the development of challenge-proven IgE-mediated food allergy.

    METHOD: We genotyped nine IL13 "tag" single nucleotide polymorphisms (tag SNPs) in 367 challenge-proven food allergic cases, 199 food-sensitized tolerant cases and 156 non-food allergic controls from the HealthNuts study. 12-month-old infants were phenotyped using open oral food challenges. SNPs were tested using Cochran-Mantel-Haenszel test adjusted for ancestry strata. A replication study was conducted in an independent, co-located sample of four paediatric cohorts consisting of 203 food allergic cases and 330 non-food allergic controls. Replication sample phenotypes were defined by clinical history of reactivity, 95% PPV or challenge, and IL13 genotyping was performed.

    RESULTS: IL13 rs1295686 was associated with challenge-proven food allergy in the discovery sample (P=.003; OR=1.75; CI=1.20-2.53). This association was also detected in the replication sample (P=.03, OR=1.37, CI=1.03-1.82) and further supported by a meta-analysis (P=.0006, OR=1.50). However, we cannot rule out an association with food sensitization. Carriage of the rs1295686 variant A allele was also associated with elevated total plasma IgE.

    CONCLUSIONS AND CLINICAL RELAVANCE: We show for the first time, in two independent cohorts, that IL13 polymorphism rs1295686 (in complete linkage disequilibrium with functional variant rs20541) is associated with challenge-proven food allergy.

    Matched MeSH terms: Th2 Cells/immunology*; Th2 Cells/pathology
  2. Targeting eosinophils in respiratory diseases: Biological axis, emerging therapeutics and treatment modalities
    Lee LY, Hew GSY, Mehta M, Shukla SD, Satija S, Khurana N, et al.
    Life Sci, 2021 Feb 15;267:118973.
    PMID: 33400932 DOI: 10.1016/j.lfs.2020.118973
    Eosinophils are bi-lobed, multi-functional innate immune cells with diverse cell surface receptors that regulate local immune and inflammatory responses. Several inflammatory and infectious diseases are triggered with their build up in the blood and tissues. The mobilization of eosinophils into the lungs is regulated by a cascade of processes guided by Th2 cytokine generating T-cells. Recruitment of eosinophils essentially leads to a characteristic immune response followed by airway hyperresponsiveness and remodeling, which are hallmarks of chronic respiratory diseases. By analysing the dynamic interactions of eosinophils with their extracellular environment, which also involve signaling molecules and tissues, various therapies have been invented and developed to target respiratory diseases. Having entered clinical testing, several eosinophil targeting therapeutic agents have shown much promise and have further bridged the gap between theory and practice. Moreover, researchers now have a clearer understanding of the roles and mechanisms of eosinophils. These factors have successfully assisted molecular biologists to block specific pathways in the growth, migration and activation of eosinophils. The primary purpose of this review is to provide an overview of the eosinophil biology with a special emphasis on potential pharmacotherapeutic targets. The review also summarizes promising eosinophil-targeting agents, along with their mechanisms and rationale for use, including those in developmental pipeline, in clinical trials, or approved for other respiratory disorders.
    Matched MeSH terms: Th2 Cells/immunology; Th2 Cells/metabolism
  3. Fulltext IL-4/IL-13 axis as therapeutic targets in allergic rhinitis and asthma
    Nur Husna SM, Md Shukri N, Mohd Ashari NS, Wong KK
    PeerJ, 2022;10:e13444.
    PMID: 35663523 DOI: 10.7717/peerj.13444
    Allergic rhinitis (AR) is a common disorder of the upper airway, while asthma is a disease affecting the lower airway and both diseases are usually comorbid. Interleukin (IL)-4 and IL-13 are critical cytokines in the induction of the pathogenic Th2 responses in AR and asthma. Targeting the IL-4/IL-13 axis at various levels of its signaling pathway has emerged as promising targeted therapy in both AR and asthma patient populations. In this review, we discuss the biological characteristics of IL-4 and IL-13, their signaling pathways, and therapeutic antibodies against each cytokine as well as their receptors. In particular, the pleiotropic roles of IL-4 and IL-13 in orchestrating Th2 responses in AR and asthma patients indicate that dual IL-4/IL-13 blockade is a promising therapeutic strategy for both diseases.
    Matched MeSH terms: Th2 Cells
  4. Fulltext Elevated interleukin-25 and its association to Th2 cytokines in systemic lupus erythematosus with lupus nephritis
    Selvaraja M, Abdullah M, Arip M, Chin VK, Shah A, Amin Nordin S
    PLoS One, 2019;14(11):e0224707.
    PMID: 31697750 DOI: 10.1371/journal.pone.0224707
    Systemic lupus erythematosus (SLE) is an autoimmune disorder that is associated with lupus nephritis, initiated by the deposition of immune complexes in the kidney; subsequently, this induces the overexpression of cytokines. Lupus nephritis is known as one of the major clinical manifestations that affect the disease severity in SLE patients. An increased number of resident periglomerular and immune cells in the kidney has the potential to affect the equilibrium of different immune cell subsets, such as Th1, Th2, Th17, and Tregs, which may be central to the induction of tissue damage in kidney by exerting either proinflammatory or anti-inflammatory effects, or both. This equilibrium has yet to be confirmed, as new players such as IL-25 remain undiscovered. IL-25 is a cytokine of the IL-17 family, which stimulates Th2-mediated immune response when overly expressed. Thus, the aim of this research is to determine the plasma levels of IL-25 and Th2-associated cytokines (IL-4, IL-5, IL-6, IL-9, IL-10, IL-13) in SLE patients with (SLE-LN) and without lupus nephritis. Sixty-four (n = 64) SLE patients and fifteen (n = 15) healthy individuals were recruited. This study demonstrated that the IL-9, IL-10 and IL-25 had significantly increased expressions in SLE-LN, followed by SLE without LN, compared to healthy controls. Meanwhile, IL-5 and IL-6 had significantly reduced. No significant difference was observed with IL-13, while the level of IL-4 was undetectable. Furthermore, IL-9 and IL-10 were significantly correlated with the IL-25, and IL-25, IL-9 and IL-10 were positively correlated with the disease severity score, SLEDAI. In conclusion, IL-25 and its associated Th2 cytokines (IL-9 and IL-10) may be involved in SLE pathogenesis. These cytokines could be potential biomarkers in monitoring and predicting the disease severity during SLE pathogenesis.
    Matched MeSH terms: Th2 Cells/immunology*
  5. Fulltext Human Invasive Muscular Sarcocystosis Induces Th2 Cytokine Polarization and Biphasic Cytokine Changes, Based on an Investigation among Travelers Returning from Tioman Island, Malaysia
    Tappe D, Slesak G, Pérez-Girón JV, Schäfer J, Langeheinecke A, Just-Nübling G, et al.
    Clin Vaccine Immunol, 2015 Jun;22(6):674-7.
    PMID: 25903356 DOI: 10.1128/CVI.00042-15
    Sarcocystis nesbitti is a parasite responsible for a biphasic eosinophilic febrile myositis syndrome in two recent outbreaks in Malaysia. We demonstrate Th2 cytokine polarization in infected travelers, an overall cytokine production decrease in the early phase of the disease suggestive of initial immunosuppression, and elevated levels of proinflammatory and chemotactic cytokines in the later myositic phase.
    Matched MeSH terms: Th2 Cells/immunology
  6. Fulltext Immunostimulatory effects of the standardized extract of Tinospora crispa on innate immune responses in Wistar Kyoto rats
    Ahmad W, Jantan I, Kumolosasi E, Bukhari SN
    Drug Des Devel Ther, 2015;9:2961-73.
    PMID: 26089645 DOI: 10.2147/DDDT.S85405
    Tinospora crispa (TC) has been used in folkloric medicine for the treatment of various diseases and has been reported for several pharmacological activities. However, the effects of TC extract on the immune system are largely unknown. Therefore, the present study was aimed to investigate the immunomodulatory effects of a standardized 80% ethanol extract of the stem of TC on innate immune responses. Male Wistar Kyoto rats were treated daily at 100 mg/kg, 200 mg/kg, and 400 mg/kg doses of the extract for 21 days by oral gavage. The immunomodulatory potential of TC was evaluated by determining its effect on chemotaxis and phagocytic activity of neutrophils isolated from the blood of rats. To further elucidate the mechanism of action, its effects on the proliferation of T- and B-lymphocytes and T-lymphocytes subsets (CD4+ and CD8+) and on the secretion of Th1 and Th2 cytokines were also monitored. The main components of the extracts, syringin and magnoflorine, were identified and quantitatively analyzed in the extracts by using a validated reversed-phase high-performance liquid chromatography method. It was observed that the chemotactic activity of neutrophils obtained from extract-treated rats increased as compared to controls. A dose-dependent increase in the number of migrated cells and phagocytosis activity of neutrophils was observed. Dose-dependent increase was also observed in the T- and B-lymphocytes proliferation stimulated with concanavalin A (5 μg/mL) and lipopolysaccharide (10 μg/mL), and was statistically significant at 400 mg/kg (P>0.01). Apart from cell-mediated immune response, the concentrations of Th1 (TNF-α, IL-2, and IFN-γ) and Th2 (IL-4) cytokines were significantly increased in sera of rats treated with different doses as compared with the control group. From these findings, it can be concluded that TC possesses immunostimulatory activity and has therapeutic potential for the prevention of immune diseases.
    Matched MeSH terms: Th2 Cells/drug effects; Th2 Cells/metabolism
  7. Fulltext Changing survival, memory cell compartment, and T-helper balance of lymphocytes between severe and mild asthma
    Abdulamir AS, Hafidh RR, Abubakar F, Abbas KA
    BMC Immunol, 2008;9:73.
    PMID: 19087256 DOI: 10.1186/1471-2172-9-73
    BACKGROUND: Asthma is a complicated network of inflammatory reactions. It is classified into mild, moderate, and severe persistent asthma. The success of asthma therapy relies much on understanding the underlying mechanisms of inflammation at each stage of asthma severity. The aim of this study was to explore the differences in apoptotic potential, CD4/CD8 ratio, memory compartment, and T- helper (Th) 1 and 2 profile of peripheral blood lymphocytes (PBL) in patients with mild intermittent asthma and severe persistent asthma during exacerbation periods.
    RESULTS: Four research lines were investigated and compared among mild asthmatics, severe asthmatics, and healthy groups by applying immunocytochemical staining of PBL. Antiapoptotic and proapoptotic proteins with Bcl-2/Bax ratio, CD4, CD8 markers with CD4+/CD8+ ratio, CD45RO+, CD45RA+ markers with memory/naive ratio (CD45RO+/CD45RA+). Th2/Th1 cytokines balance represented by IL-4/IFN-gamma ratio was measured by enzyme-linked immunosorbent assay (ELISA) for in vitro PBL cytokine synthesis. It was found that Bcl-2/Bax ratio was higher in severe than in mild asthmatics which in turn was higher than in healthy group. And memory/naive ratio of PBL was higher in severe than in mild asthmatics. Moreover, memory cells, CD45RO+ and CD45RO+/CD45RA+ ratio were correlated directly with Bcl-2/Bax, in severe and mild asthma patients. In contrast, CD4+/CD8+ ratio was not changed significantly among healthy group, mild and severe asthmatics. However, CD8+ cells were correlated directly with memory cells, CD45RO+, in severe asthmatics only. Interestingly, the dominant profile of cytokines appeared to change from T helper 2 (Th2) in mild asthmatics to T helper 1 (Th1) in severe asthmatics where the lowest in vitro IL-4/IFN-gamma ratio and highest IFN-gamma were found.
    CONCLUSION: It was concluded that the underlying mechanisms of inflammation might vary greatly with asthma stage of severity. Mild intermittent asthma is mainly Th2 allergen-oriented reaction during exacerbations with good level of apoptosis making the inflammation as self-limiting, while in severe persistent asthma, the inflammatory reaction mediated mainly by Th1 cytokines with progressive loss of apoptosis leading to longer exacerbations, largely expanded memory cells, CD45RO+, leading to persistent baseline inflammation.
    Matched MeSH terms: Th2 Cells/immunology; Th2 Cells/metabolism*; Th2 Cells/pathology
  8. Fulltext IL-4 enhances IL-10 production in Th1 cells: implications for Th1 and Th2 regulation
    Mitchell RE, Hassan M, Burton BR, Britton G, Hill EV, Verhagen J, et al.
    Sci Rep, 2017 Sep 12;7(1):11315.
    PMID: 28900244 DOI: 10.1038/s41598-017-11803-y
    IL-10 is an immunomodulatory cytokine with a critical role in limiting inflammation in immune-mediated pathologies. The mechanisms leading to IL-10 expression by CD4(+) T cells are being elucidated, with several cytokines implicated. We explored the effect of IL-4 on the natural phenomenon of IL-10 production by a chronically stimulated antigen-specific population of differentiated Th1 cells. In vitro, IL-4 blockade inhibited while addition of exogenous IL-4 to Th1 cultures enhanced IL-10 production. In the in vivo setting of peptide immunotherapy leading to a chronically stimulated Th1 phenotype, lack of IL-4Rα inhibited the induction of IL-10. Exploring the interplay of Th1 and Th2 cells through co-culture, Th2-derived IL-4 promoted IL-10 expression by Th1 cultures, reducing their pathogenicity in vivo. Co-culture led to upregulated c-Maf expression with no decrease in the proportion of T-bet(+) cells in these cultures. Addition of IL-4 also reduced the encephalitogenic capacity of Th1 cultures. These data demonstrate that IL-4 contributes to IL-10 production and that Th2 cells modulate Th1 cultures towards a self-regulatory phenotype, contributing to the cross-regulation of Th1 and Th2 cells. These findings are important in the context of Th1 driven diseases since they reveal how the Th1 phenotype and function can be modulated by IL-4.
    Matched MeSH terms: Th2 Cells
  9. Fulltext Contribution of IL-33/ILC2-mediated Th2 cytokines during the progression of minimal change disease
    Liu C, Liu L, Huang Y, Shi R, Wu Y, Hakimah Binti Ismail I
    Int Immunopharmacol, 2023 Jan;114:109493.
    PMID: 36527879 DOI: 10.1016/j.intimp.2022.109493
    Minimal change disease (MCD) is a common type of nephrotic syndrome with high recurrence rate. This study aims to explore the impacts of interleukin (IL)-33 in MCD and to discuss its potential mechanism. In adriamycin (ADM) and puromycin aminonucleoside (PAN)-induced MCD rat model, IL-33 was used for treatment. H&E staining was applied for detecting histological changes. Critical proteins were examined by western blot. Corresponding commercial kits tested oxidative stress- and inflammation-related factors. Cell apoptosis was measured by TUNEL assay. ADM-induced podocyte injury model was establish to mimic MCD in vitro. Cell proliferation and apoptosis were detected by CCK-8 and TUNEL assays. Finally, podocyte was stimulated by innate lymphoid type-2 cells-secreted Th2 cytokines (ILC2s: IL-13 and IL-5 respectively), with or without incubation with M1 macrophage medium to further explore the immune-regulation of ILC2s behind the inflammatory environment of MCD. It was found that PAN-induced kidney jury, inflammation, oxidative stress and apoptosis were severer than ADM, and IL-33 treatment significantly alleviated the above injuries in PAN and ADM-induced MCD rat model. Moreover, IL-33 reversed the reduced viability and increased oxidative stress and apoptosis in ADM-induced podocyte injury model. Further, the capacities of IL-13 alone in inducing M1/M2 macrophage polarization, apoptosis, inflammation, kidney injury and reducing cell viability are stronger than IL-5. However, IL-13 reversed reduced cell viability and stimulated apoptosis, inflammation, kidney injury mediated by co-incubation with M1-conditioned medium. Collectively, IL-33 might protect against immunologic injury in MCD via mediating ILC2s-secreted IL-13.
    Matched MeSH terms: Th2 Cells
  10. Relationship between various cytokines implicated in asthma
    Ayakannu R, Abdullah NA, Radhakrishnan AK, Lechimi Raj V, Liam CK
    Hum Immunol, 2019 Sep;80(9):755-763.
    PMID: 31054782 DOI: 10.1016/j.humimm.2019.04.018
    Asthma is a complex disorder involving immunologic, environmental, genetic and other factors. Today, asthma is the most common disease encountered in clinical medicine in both children and adults worldwide. Asthma is characterized by increased responsiveness of the tracheobronchial tree resulting in chronic swelling and inflammation of the airways recognized to be controlled by the T-helper 2 (Th2) lymphocytes, which secrete cytokines to increase the production of IgE by B cells. There are many cytokines implicated in the development of the chronic inflammatory processes that are often observed in asthma. Ultimately, these cytokines cause the release of mediators such as histamine and leukotrienes (LT), which in turn promote airway remodeling, bronchial hyperresponsiveness and bronchoconstriction. The CD4+ T-lymphocytes from the airways of asthmatics express a panel of cytokines that represent the Th2 cells. The knowledge derived from numerous experimental and clinical studies have allowed physicians and scientists to understand the normal functions of these cytokines and their roles in the pathogenesis of asthma. The main focus of this review is to accentuate the relationship between various cytokines implicated in human asthma. However, some key findings from animal models will be highlighted to support the discoveries from clinical studies.
    Matched MeSH terms: Th2 Cells/immunology
  11. Fulltext Differential polarization and the expression of efferocytosis receptor MerTK on M1 and M2 macrophages isolated from coronary artery disease patients
    Mohd Idrus FN, Ahmad NS, Hoe CH, Azlan M, Norfuad FA, Yusof Z, et al.
    BMC Immunol, 2021 03 24;22(1):21.
    PMID: 33761885 DOI: 10.1186/s12865-021-00410-2
    BACKGROUND: Differential polarization of macrophage into M1 and M2 mediates atherosclerotic plaque clearance through efferocytosis. Higher expression of Mer proto-oncogene tyrosine kinase (MerTK) on M2 macrophage helps in maintaining macrophage efferocytic efficiency. In healthy individuals, macrophage polarization into M1 and M2 occurs in tissues in concomitance with the acquisition of functional phenotypes depending on specific microenvironment stimuli. However, whether the macrophage differential polarization and MerTK expression vary in coronary artery disease (CAD) patients remain unknown.

    OBJECTIVE: This study aimed to elucidate the polarization of M1 and M2 macrophage from CAD patients as well as to investigate the expression of MerTK in these macrophage phenotypes.

    METHODS: A total of 14 (n) CAD patients were recruited and subsequently grouped into "no apparent CAD", "non-obstructive CAD" and "obstructive CAD" according to the degree of stenosis. Thirty ml of venous blood was withdrawn to obtain monocyte from the patients. The M1 macrophage was generated by treating the monocyte with GMCSF, LPS and IFN-γ while MCSF, IL-4 and IL-13 were employed to differentiate monocyte into M2 macrophage. After 7 days of polarization, analysis of cell surface differentiation markers (CD86+/CD80+ for M1 and CD206+/CD200R+ for M2) and measurement of MerTK expression were performed using flow cytometry.

    RESULTS: Both M1 and M2 macrophage expressed similar level of CD86, CD80 and CD206 in all groups of CAD patients. MerTK expression in no apparent CAD patients was significantly higher in M2 macrophage compared to M1 macrophage [12.58 ± 4.40 vs. 6.58 ± 1.37, p = 0.040].

    CONCLUSION: Differential polarization of macrophage into M1 and M2 was highly dynamic and can be varied due to the microenvironment stimuli in atherosclerotic plaque. Besides, higher expression of MerTK in patients with the least coronary obstructive suggest its vital involvement in efferocytosis.

    Matched MeSH terms: Th2 Cells/immunology
  12. Development of two salmonella-based oral vaccines against human respiratory syncytial virus
    Azizi Jalilian F, Yusoff K, Suhaimi S, Amini R, Sekawi Z, Jahanshiri F
    J Biol Regul Homeost Agents, 2015 Jan-Mar;29(1):7-18.
    PMID: 25864737
    Human respiratory syncytial virus is the most common cause of bronchiolitis and other respiratory infections in infants and the elderly worldwide. We have developed two new oral vaccines using Salmonella typhi TY21a to carry and express the immunogenic epitopes of RSV fusion (F) and attachment (G) glycoproteins on its surface, separately. To evaluate the efficacy of the designed vaccines, BALB/c mice were orally immunized and then infected with RSV. Immune response analyses showed that cellmediated, mucosal and humoral immunity in the vaccinated mice were significantly enhanced compared to the control group. Both vaccines generated a balanced Th1/Th2 immune response which is crucial for efficiency of vaccines against RSV. Furthermore, histopathological examination proved that these vaccines were safe as they did not cause any Th2-associated adverse effects in the lungs of RSV-infected mice. The findings of this research suggest that Salmonella-F and Salmonella-G vaccine candidates may have strong potential to prevent RSV infection.
    Matched MeSH terms: Th2 Cells/drug effects; Th2 Cells/immunology
  13. Phytosterols isolated from Clinacanthus nutans induce immunosuppressive activity in murine cells
    Le CF, Kailaivasan TH, Chow SC, Abdullah Z, Ling SK, Fang CM
    Int Immunopharmacol, 2017 Mar;44:203-210.
    PMID: 28119186 DOI: 10.1016/j.intimp.2017.01.013
    Clinacanthus nutans (Burm. f.) Lindau is a traditional medicinal plant belonging to the Acanthaceae family. Its therapeutic potentials have been increasingly documented particularly the antiviral activity against Herpes Simplex Virus (HSV), anti-cancer, anti-oxidant, anti-inflammatory and immunomodulatory activities. However, majority of these studies used crude or fractionated extracts and not much is known about individual compounds from these extracts and their biological activities. In the present study, we have isolated four compounds (CN1, CN2, CN3 and CN4) from the hexane fractions of C. nutans leaves. Using NMR spectroscopic analysis, these compounds were identified to be shaftoside (CN1), stigmasterol (CN2), β-sitosterol (CN3) and a triterpenoid lupeol (CN4). To determine the immunosuppressive potential of these compounds, their effects on mitogens induced T and B lymphocyte proliferation and the secretion of helper T cell cytokines were examined. Among the four compounds, stigmasterol (CN2) and β-sitosterol (CN3) were shown to readily inhibit T cell proliferation mediated by Concanavalin A (ConA). However, only β-sitosterol (CN3) and not stigmasterol (CN2) blocks the secretion of T helper 2 (Th2) cytokines (IL-4 and IL-10). Both compounds have no effect on the secretion of Th1 cytokines (IL-2 and IFN-γ), suggesting that β-sitosterol treatment selectively suppresses Th2 activity and promotes a Th1 bias. CN3 was also found to significantly reduce the proliferation of both T helper cells (CD4(+)CD25(+)) and cytotoxic T cells (CD8(+)CD25(+)) following T cell activation induced by ConA. These results suggested that phytosterols isolated from C. nutans possess immunomodulatory effects with potential development as immunotherapeutics.
    Matched MeSH terms: Th2 Cells/drug effects*; Th2 Cells/immunology
  14. Effect of colchicine on the murine immune response induced by Aggregatibacter actinomycetemcomitans
    Sosroseno W
    Biomed Pharmacother, 2009 Mar;63(3):221-7.
    PMID: 18534811 DOI: 10.1016/j.biopha.2008.04.004
    The aim of the present study was to test the hypothesis that colchicine may alter Aggregatibacter actinomycetemcomitans-induced immune response and abscess formation in mice. BALB/c mice were either sham-immunized or immunized with heat-killed A. actinomycetemcomitans. Spleen cells were stimulated with heat-killed A. actinomycetemcomitans in the presence or absence of colchicine. Specific IgG subclass antibodies, interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and cell proliferation were determined. The animals were sham-immunized (group I) or immunized with heat-killed A. actinomycetemcomitans (groups II-VII). Colchicine was administered intraperitoneally before (group III), on the same day of (group IV), or after (group V) the primary immunization and on the same day of (group VI) or after (group VII) the secondary immunization. All groups were challenged with viable A. actinomycetemcomitans. The levels of serum-specific IgG subclasses and both IFN-gamma and IL-4 before and after bacterial challenge were assessed. The diameter of skin lesions was assessed. The results showed that colchicine augmented splenic-specific IgG1 and IL-4 as well as cell proliferation but suppressed specific IgG2a and IFN-gamma levels. Enhancement of serum-specific IgG1 and IL-4 levels, suppression of specific IgG2a and IFN-gamma levels as well as DTH response, and delayed healing of the lesions were observed in groups IV and VI, but not in the remaining groups of animals. Therefore, these results suggest that colchicine may induce a T helper 2 (Th2)-like immunity specific to A. actinomycetemcomitans in vitro and that colchicine administered on the same day as the immunization may stimulate a non-protective Th2-like immunity in A. actinomycetemcomitans-induced infections in mice.
    Matched MeSH terms: Th2 Cells/immunology*
  15. Fulltext Genetic Diversity and Natural Selection of the Plasmodium knowlesi Circumsporozoite Protein Nonrepeat Regions
    Fong MY, Ahmed MA, Wong SS, Lau YL, Sitam F
    PLoS One, 2015;10(9):e0137734.
    PMID: 26379157 DOI: 10.1371/journal.pone.0137734
    Plasmodium knowlesi is a simian malaria parasite that has been identified to cause malaria in humans. To date, several thousand cases of human knowlesi malaria have been reported around Southeast Asia. Thus far, there is no detailed study on genetic diversity and natural selection of P. knowlesi circumsporozoite protein (CSP), a prominent surface antigen on the sporozoite of the parasite. In the present study, the genetic diversity and natural selection acting on the nonrepeat regions of the gene encoding P. knowlesi CSP were investigated, focusing on the T-cell epitope regions at the C-terminal of the protein.
    Matched MeSH terms: Th2 Cells/immunology
  16. Increase of Plasma TNF-α Is Associated with Decreased Levels of Blood Platelets in Clinical Dengue Infection
    Meena AA, Murugesan A, Sopnajothi S, Yong YK, Ganesh PS, Vimali IJ, et al.
    Viral Immunol, 2019 09 18;33(1):54-60.
    PMID: 31532346 DOI: 10.1089/vim.2019.0100
    Dengue virus (DENV) infection has become an increasingly common concern in tropical and subtropical regions. It has protean manifestations ranging from febrile phase to severe life-threatening illness. In this study, we estimated Th1 and Th2 cytokines and correlated the levels with dengue severity along with certain hematological and biochemical parameters. We also studied the seroprevalence of dengue between October and December 2017 at the Government Theni Medical College, India. Individuals with dengue fever (DF) were positive for either IgM or IgG, or both. The biochemical and hematological parameters along with plasma tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), granulocyte monocyte-colony stimulating factor (GM-CSF), interleukin (IL)-13, IL-12p70, IL-10, IL-5, IL-4, and IL-2 cytokines were estimated. The prevalence of DF was 42.9% during the study period. IL-2, TNF-α, IL-4, and IL-10 levels were significantly elevated (p 
    Matched MeSH terms: Th2 Cells/immunology
  17. Current Trend in Immunotherapy for Peanut Allergy
    Joo Chan C, Richardo T, Lim RLH
    Int Rev Immunol, 2018;37(6):279-290.
    PMID: 30638084 DOI: 10.1080/08830185.2018.1509967
    Peanut allergy is a hypersensitivity reaction with symptoms varying from mild to severe anaphylaxis, tends to be lifelong and very few are able to outgrow this allergy. The prevalence of peanut allergy is highest among the Western countries and over the past decade, a 3.5 fold increase in prevalence of peanut allergy was reported among children in the United States. Increasing prevalence has also been observed among the Asian countries. As with other food allergies, peanut allergy reduces quality of life for the affected individuals and the social and economy burden of healthcare for peanut allergy is substantial. To date, there is no effective treatment for peanut allergy and disease management is by avoidance or relieve of symptoms via administration of epinephrine. Peanut allergy is a type-1 hypersensitivity reaction due to specific IgE production by activated T-helper type 2 (TH2) cells. Studies on various immunotherapy routes such as oral immunotherapy (OIT), sublingual immunotherapy and epicutaneous immunotherapy trials using peanut have shown the ability to induce desensitisation, shifting the allergen-specific cytokine production away from a TH2 respond. In the recent years, lactic acid bacteria probiotics have been reported to down-regulate allergy due to its inherent immunomodulatory properties. Wild-type probiotic in combination with peanut proteins or recombinant probiotics harbouring peanut allergens have been explored for OIT due to its ability to down-regulate allergen-specific-IgE production and the TH2 responses, while increasing the beneficiary population of TH1 regulatory T cells (Treg). This review discusses the current strategies in immunotherapy for peanut allergy.
    Matched MeSH terms: Th2 Cells/immunology
  18. Systemic Predictors of Eosinophilic Chronic Rhinosinusitis
    Ho J, Hamizan AW, Alvarado R, Rimmer J, Sewell WA, Harvey RJ
    Am J Rhinol Allergy, 2018 Jul;32(4):252-257.
    PMID: 29862828 DOI: 10.1177/1945892418779451
    Background Eosinophilic chronic rhinosinusitis (eCRS) is linked with skewed T-helper 2 or immunoglobulin E (IgE)-mediated allergic responses, with differing diagnosis, prognosis, and management to non-eCRS. Objective The association between biomarkers and eCRS was investigated to assess the predictors of eCRS. Methods A cross-sectional study of adult patients with chronic rhinosinusitis (CRS) undergoing endoscopic sinus surgery was conducted. eCRS was defined by histopathological assessment showing >10 eosinophils/high-power field on sinus mucosal biopsy. Blood tests were performed preoperatively and assessed for a full blood count including eosinophils and a white cell count (WCC) as well as biochemical markers of inflammation and atopy including Immunoglobulin E (IgE), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and ImmunoCAP testing for serum-specific IgE. Comparisons between eCRS and non-eCRS patients were performed. Results 345 patients (48.1% female, age 48.72 ± 15.06 years) were recruited, with 206 (59.7%) identified as eCRS, 41% with asthma and 47% CRS with nasal polyps. eCRS patients were more likely to have asthma ( P 0.24 × 109/L), eosinophil ratio (>4.27% of total WCC), and lower ESR when compared with non-eCRS.
    Matched MeSH terms: Th2 Cells/immunology*
  19. Role of cytokines produced by T helper immune-modulators in dengue pathogenesis: a systematic review and meta-analysis
    Tran L, Radwan I, Minh LHN, Low SK, Hashan MR, Gomaa MD, et al.
    Acta Trop, 2021 Jan 06.
    PMID: 33421421 DOI: 10.1016/j.actatropica.2021.105823
    BACKGROUND AND OBJECTIVES: Modulation of the immune reaction is essential in the development of various diseases, including dengue's "Cytokine Tsunami", an increase in vascular permeability with concomitant severe vascular leakage. We aim to identify the role of T-helper (Th) cells, Th2 and Th7, with their related cytokines in dengue pathogenesis.

    MATERIAL AND METHODS: Nine electronic databases and manual search were applied to detect available publications. A meta-analysis using a fixed- or random-effect model was performed to measure standardized mean difference (SMD) with 95% confidence interval (CI). The National Institute of Health (NIH) tools for observational cohort, cross-sectional, and case-control studies were used to examine the risk of bias. The protocol was recorded in PROSPERO with CRD42017060230.

    RESULTS: A total of 38 articles were found including 19 case-control, 11 cross-sectional and 8 prospective cohort studies. We indicated that Th2 cytokines (IL-4, IL-6, IL-8) and Th17 cytokine (IL-17) in dengue patients were notably higher than in a healthy control group in acute phase (SMD = 1.59, 95% CI [0.68, 2.51], p = 0.001; SMD = 1.24, 95% CI [0.41, 2.06], p = 0.003; SMD = 1.13, 95% CI [0.61, 1.66], p<0.0001; SMD = 1.74, 95% CI [0.87, 2.61], p<0.0001), respectively.

    CONCLUSIONS: This study provides evidence of the significant roles of IL-4, IL-6, IL-8, IL-10 and IL-17 in the pathogenesis of developing a severe reaction in dengue fever. However, to fully determine the association of Th cytokines with dengue, it is necessary to perform further studies to assess kinetic levels during the duration of the illness.

    Matched MeSH terms: Th2 Cells
  20. Emerging concepts and directed therapeutics for the management of asthma: regulating the regulators
    Shastri MD, Chong WC, Dua K, Peterson GM, Patel RP, Mahmood MQ, et al.
    Inflammopharmacology, 2021 Feb;29(1):15-33.
    PMID: 33152094 DOI: 10.1007/s10787-020-00770-y
    Asthma is a common, heterogeneous and serious disease, its prevalence has steadily risen in most parts of the world, and the condition is often inadequately controlled in many patients. Hence, there is a major need for new therapeutic approaches. Mild-to-moderate asthma is considered a T-helper cell type-2-mediated inflammatory disorder that develops due to abnormal immune responses to otherwise innocuous allergens. Prolonged exposure to allergens and persistent inflammation results in myofibroblast infiltration and airway remodelling with mucus hypersecretion, airway smooth muscle hypertrophy, and excess collagen deposition. The airways become hyper-responsive to provocation resulting in the characteristic wheezing and obstructed airflow experienced by patients. Extensive research has progressed the understanding of the underlying mechanisms and the development of new treatments for the management of asthma. Here, we review the basis of the disease, covering new areas such as the role of vascularisation and microRNAs, as well as associated potential therapeutic interventions utilising reports from animal and human studies. We also cover novel drug delivery strategies that are being developed to enhance therapeutic efficacy and patient compliance. Potential avenues to explore to improve the future of asthma management are highlighted.
    Matched MeSH terms: Th2 Cells
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