Galápagos iguanas are a monophyletic group endemic to the Galápagos archipelago, comprising the marine iguana Amblyrhynchus cristatus and three species of land iguanas: Conolophus subcristatus, C. pallidus and C. marthae. The biogeographic history of the land species in relation to their current distributions remains uncertain, in particular the origins of C. marthae, which is restricted to a small area of the northern part of Isabela Island. The classification of C. pallidus as a separate species has also been debated. We analyzed DNA sequences (RADseq) to reconstruct demographic histories of selected local populations of all Galápagos iguana species and estimate their divergence times within a multispecies coalescent framework. Our results indicate an early date for the colonization of Galápagos by iguanas, relative to island formation, at ca. 10 Mya, and support a recent split of C. marthae via allopatric speciation, after the emergence of Isabela Island, at ca. 0.57 Mya. We find contrasting demographic histories in C. marthae and the syntopic population of C. subcristatus, suggesting competitive interaction between these species. We also confirm that the divergence of C. pallidus from C. subcristatus is recent (0.09 Mya) and close in time to the split between populations of C. subcristatus from different islands. Our genetic data support recent census estimates indicating a relatively small current effective population size (Ne) in all the studied populations. Our findings shed light on the evolutionary history of Galápagos iguanas and emphasize the need for targeted conservation strategies.
Psoriasis is an immune-mediated skin disorder associated with severe systemic comorbidities. Whereas IL-36 is a key disease driver, the pathogenic role of this cytokine has mainly been investigated in skin. Thus, its effects on systemic immunity and extracutaneous disease manifestations remain poorly understood. To address this issue, we investigated the consequences of excessive IL-36 activity in circulating immune cells. We initially focused our attention on generalized pustular psoriasis (GPP), a clinical variant associated with pervasive upregulation of IL-36 signaling. By undertaking blood and neutrophil RNA sequencing, we demonstrated that affected individuals display a prominent IFN-I signature, which correlates with abnormal IL-36 activity. We then validated the association between IL-36 deregulation and IFN-I over-expression in patients with severe psoriasis vulgaris (PV). We also found that the activation of IFN-I genes was associated with extracutaneous morbidity, in both GPP and PV. Finally, we undertook mechanistic experiments, demonstrating that IL-36 acts directly on plasmacytoid dendritic cells, where it potentiates toll-like receptor (TLR)-9 activation and IFN-α production. This effect was mediated by the upregulation of PLSCR1, a phospholipid scramblase mediating endosomal TLR-9 translocation. These findings identify an IL-36/ IFN-I axis contributing to extracutaneous inflammation in psoriasis.