Anti-IL17A monoclonal antibody, clone UD22-9I5 [Biotin]

Atopic dermatitis (AD) is a multi-factorial skin disease with a complex inflammatory signature including type 2 and type 17 activation. Although colonization by S. aureus is common in AD, the mechanisms rendering an organism prone to dysbiosis, and the role of IL-17A in the control of S. aureus-induced skin inflammation, are not well understood. Here, we show several pathological aspects of AD, including type 2/type 17 immune responses, elevated IgE, barrier dysfunction, pruritus, and importantly, spontaneous S. aureus colonization in JunB(Delta ep) mice, with a large transcriptomic overlap with AD. Additionally, using Rag1(-/-) mice, we demonstrate that adaptive immune cells are necessary for protection against S. aureus colonization. Prophylactic antibiotics, but not antibiotics after established dysbiosis, reduce IL-17A expression and skin inflammation, examined using Il17a-eGFP reporter mice. Mechanistically, keratinocytes lacking JunB exhibit higher MyD88 levels in vitro and in vivo, previously shown to regulate S. aureus colonization. In conclusion, our data identify JunB as an upstream regulator of microbiota-immune cell interactions and characterize the IL-17A response upon spontaneous dysbiosis.

Background: Rheumatoid Arthritis (RA) is an autoimmune systemic disease and in its pathogenesis participate several proinflammatory cytokines, including those produced by Th17 cells. We performed a systematic review aiming to assess the associations between polymorphisms in Th17 cytokines, namely IL-17A, IL-17F, IL-21 and IL-22, and susceptibility to RA. Methods: We searched three electronic databases (MEDLINE, Scopus and Web of Science) for observational studies assessing the association between susceptibility to RA (or its clinical presentation) and polymorphisms of the cytokines IL-17A, IL-17F, IL-21 and IL-22. From the selected studies, we extracted information on the studied polymorphisms, assessed outcomes, and demographic characteristics of participants. We performed random effects meta-analyses assessing the associations between susceptibility to RA and different genotypes of the IL17A rs2275913, IL-17F rs763780 and IL-17F rs2397084 polymorphisms. Primary studies' quality was assessed using the Q-Genie tool. Results: Fifteen studies were included in this systematic review. Five IL-17A polymorphisms were reported to be associated with susceptibility to RA. For the IL-17A rs2275913 polymorphism, our meta-analysis showed the AA genotype to be significantly associated with lower susceptibility to RA (OR = 0.76; 95%CI = 0.61-0.93; p = 0.01), while the opposite was observed for the GG genotype (OR = 1.20; 95%CI = 1.06-1.35; p = 0.01). Concerning IL-17F rs763780 polymorphism, the TT genotype was found to be significantly less frequent in RA patients (OR = 0.49; 95%CI = 0.31-0.77; p = 0.002), while the opposite was observed for the CT genotype (OR = 2.00; 95%CI = 1.03-3.87; p = 0.04). No significant associations were found regarding rs2397084 polymorphisms. For IL-21, rs6822844 and rs4505848 were described to have significant associations with susceptibility to RA. No studies were found assessing IL-22 polymorphisms in RA. Conclusions: IL-17A rs2275913 and IL-17F rs763780 polymorphisms are significantly associated with susceptibility to RA and with different clinical characteristics of this disease.