Colitis alters the antigen-specific response to skin commensal bacteria and predisposes to neutrophilic skin inflammation
Journal of Investigative Dermatology(2021)
摘要
Abstract Both gut and skin house microbial communities capable of influencing host immunity. During homeostasis, resident microbes are thought to have a dominant impact on local immune cell function. However, the prevalence of skin disorders among IBD patients suggests that this compartmentalized control may not hold under disease conditions. We hypothesize that an altered immune response to gut-resident microbes during colitis may facilitate excessive inflammation directed at skin commensals. Our lab has previously shown that colonization of neonatal mice with Staphylococcus epidermidis expressing the model antigen 2W (S. epi-2W) results in establishment of tolerance, as denoted by a higher percentage of 2W-specific regulatory T cells (Tregs) in the skin and skin-draining lymph nodes (SDLNs) and fewer skin neutrophils upon later-life S. epi-2W re-exposure. To test whether colitis perturbs tolerance to commensal skin bacteria, we colonized mice with S. epi-2W as neonates and subjected them to colitis as adults in conjunction with re-exposure. Colitic mice exhibited increased skin neutrophils and reduced percentages of S. epi-specific Tregs in skin and SDLNs compared to controls. Notably, no difference in S. epi-specific Tregs was noted in mice subjected to LPS-induced sepsis. Increased intra-intestinal presence of S. epi-2W during colitis indicates initiation of this response in the gut. Consistent with this, adoptive transfer experiments revealed a colitis-induced increase in CD4+ T cell trafficking from gut-draining LN to SDLNs. Recovery of S. epi-specific Tregs in colitic Cd4CreIl1r1flox/flox mice indicates an additional role for circulating IL-1 cytokines in shaping the skin commensal response during colitis.
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关键词
skin commensal bacteria,antigen-specific
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