Mucosal Immunology Laboratory, Department of Convergence Medicine, University of Ulsan College of Medicine/Asan Medical Center, Seoul, Korea.
ASAN Institute for Life Science, Asan Medical Center, Seoul, Korea.
Sci Rep. 2017 Jul 24;7(1):6348. doi: 10.1038/s41598-017-05740-z.
IκBζ, which is encoded by the Nfkbiz gene, is a member of the nuclear IκB family of proteins that act as transcriptional regulators via association with NF-κB. Nfkbiz-deficient (Nfkbiz ) mice develop spontaneous dermatitis; however, the underlying mechanism has yet to be elucidated. In our study, we found higher skin pathology scores and more serum IgE antibodies and trans-epidermal water loss in Nfkbiz than in Nfkbiz-sufficient (Nfkbiz ) mice. There was also greater expansion of IFN-γ-, IL-17A-, and IL-22-secreting CD4 T cells and of IL-17A-secreting γδ T cells in the skin of Nfkbiz mice than in with Nfkbiz mice. Pyrosequencing analysis showed decreased diversity of resident bacteria and markedly expanded Staphylococcus (S.) xylosus in the skin of Nfkbiz mice. Oral administration of antibiotics including cephalexin and enrofloxacin ameliorated skin inflammation. Topical application of S. xylosus also resulted in the expansion of IL-17A-secreting CD4 T cells along with high levels of pro-inflammatory cytokines and chemokines in the skin of Nfkbiz mice. The expansion of commensal S. xylosus may be one cause of skin dysbiosis in Nfkbiz mice and suggests that the Nfkbiz gene may play a regulatory role in the microbiota-skin immunity axis.
IκBζ，由 Nfkbiz 基因编码，是核 IκB 蛋白家族的成员之一，通过与 NF-κB 结合发挥转录调节因子的作用。Nfkbiz 缺陷（Nfkbiz ）小鼠自发发生皮炎；然而，其潜在机制尚未阐明。在我们的研究中，我们发现 Nfkbiz 小鼠的皮肤病理评分更高，血清 IgE 抗体和经皮水分丢失更多。Nfkbiz 小鼠皮肤中 IFN-γ+、IL-17A+和 IL-22+分泌的 CD4 T 细胞以及 IL-17A+分泌的 γδ T 细胞也有更大的扩增。焦磷酸测序分析显示 Nfkbiz 小鼠皮肤中常驻细菌的多样性降低，金黄色葡萄球菌（S.）明显扩张。包括头孢氨苄和恩诺沙星在内的抗生素的口服给药可改善皮肤炎症。S. xylosus 的局部应用也导致 Nfkbiz 小鼠皮肤中 IL-17A+分泌的 CD4 T 细胞的扩增，同时伴有高水平的促炎细胞因子和趋化因子。共生 S. xylosus 的扩张可能是 Nfkbiz 小鼠皮肤微生态失调的一个原因，并表明 Nfkbiz 基因可能在微生物群-皮肤免疫轴中发挥调节作用。
