Department of Dermatology, Heidelberg University Hospital, Heidelberg, Germany; Institute for Molecular Medicine, Paul Klein Center for Immune Intervention, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
Institute for Molecular Medicine, Paul Klein Center for Immune Intervention, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
J Invest Dermatol. 2023 Jul;143(7):1257-1267.e10. doi: 10.1016/j.jid.2023.01.016. Epub 2023 Feb 2.
Keratinocytes (KCs) form the outer epithelial barrier of the body, protecting against invading pathogens. Mice lacking the IL-17RA or both IL-17A and IL-17F develop spontaneous Staphylococcusaureus skin infections. We found a marked expansion of T cells, comprised of RORγt-expressing γδ T cells and T helper 17 cells in the skin-draining lymph nodes of these mice. Contradictory to previous suggestions, this expansion was not a result of a direct negative feedback loop because we found no expansion of T cells in mice lacking IL-17 signaling specifically in T cells. Instead, we found that the T expansion depended on the microbiota and was observed only when KCs were deficient for IL-17RA signaling. Indeed, mice that lack IL-17RA only in KCs showed an increased susceptibility to experimental epicutaneous infection with S. aureus together with an accumulation of IL-17A-producing γδ T cells. We conclude that deficiency of IL-17RA on KCs leads to microbiota dysbiosis in the skin, which triggers the expansion of IL-17A-producing T cells. Our data show that KCs are the primary target cells of IL-17A and IL-17F, coordinating the defense against microbial invaders in the skin.
角质形成细胞 (KCs) 形成身体的外部上皮屏障，防止入侵病原体。缺乏 IL-17RA 或同时缺乏 IL-17A 和 IL-17F 的小鼠会自发发生金黄色葡萄球菌皮肤感染。我们发现这些小鼠的皮肤引流淋巴结中 T 细胞明显扩张，包括表达 RORγt 的 γδ T 细胞和辅助性 17 细胞。与之前的建议相反，这种扩张不是由于直接的负反馈回路引起的，因为我们在缺乏 IL-17 信号的特异性在 T 细胞中缺乏 T 细胞的小鼠中没有发现 T 细胞的扩张。相反，我们发现 T 细胞的扩张取决于微生物群，并且仅在 KCs 缺乏 IL-17RA 信号时才观察到。事实上，仅在 KCs 中缺乏 IL-17RA 的小鼠在实验性表皮感染金黄色葡萄球菌时表现出易感性增加，同时积累了产生 IL-17A 的 γδ T 细胞。我们得出结论，KCs 上的 IL-17RA 缺乏会导致皮肤微生物群失调，从而触发产生 IL-17A 的 T 细胞的扩张。我们的数据表明，KCs 是 IL-17A 和 IL-17F 的主要靶细胞，协调皮肤中针对微生物入侵者的防御。
