The resident pathobiont Staphylococcus xylosus in Nfkbiz-deficient skin accelerates spontaneous skin inflammation

Abstract 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 o...

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Autores principales: Yeji Kim, Yong-Soo Lee, Jin-Young Yang, Su-Hyun Lee, Yun-Yong Park, Mi-Na Kweon
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/029952512e8a468ebc00e61a7f5021d9
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Sumario:Abstract 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.