@article{7b1d98a224f040d385d7faddec147f42,
title = "Staphylococcus cohnii is a potentially biotherapeutic skin commensal alleviating skin inflammation",
abstract = "Host-microbe interactions orchestrate skin homeostasis, the dysregulation of which has been implicated in chronic inflammatory conditions such as atopic dermatitis and psoriasis. Here, we show that Staphylococcus cohnii is a skin commensal capable of beneficially inhibiting skin inflammation. We find that Tmem79−/− mice spontaneously develop interleukin-17 (IL-17)-producing T-cell-driven skin inflammation. Comparative skin microbiome analysis reveals that the disease activity index is negatively associated with S. cohnii. Inoculation with S. cohnii strains isolated from either mouse or human skin microbiota significantly prevents and ameliorates dermatitis in Tmem79−/− mice without affecting pathobiont burden. S. cohnii colonization is accompanied by activation of host glucocorticoid-related pathways and induction of anti-inflammatory genes in the skin and is therefore effective at suppressing inflammation in diverse pathobiont-independent dermatitis models, including chemically induced, type 17, and type 2 immune-driven models. As such, S. cohnii strains have great potential as effective live biotherapeutics for skin inflammation.",
keywords = "atopic dermatitis, biotherapy, psoriasis, skin microbiome",
author = "Yoshihiro Ito and Takashi Sasaki and Youxian Li and Takeshi Tanoue and Yuki Sugiura and Skelly, {Ashwin N.} and Wataru Suda and Yusuke Kawashima and Nobuyuki Okahashi and Eiichiro Watanabe and Hiroto Horikawa and Aiko Shiohama and Rina Kurokawa and Eiryo Kawakami and Hachiro Iseki and Hiroshi Kawasaki and Yoichiro Iwakura and Atsushi Shiota and Liansheng Yu and Junzo Hisatsune and Haruhiko Koseki and Motoyuki Sugai and Makoto Arita and Osamu Ohara and Takeshi Matsui and Makoto Suematsu and Masahira Hattori and Koji Atarashi and Masayuki Amagai and Kenya Honda",
note = "Funding Information: K.H. was funded through AMED LEAP under grant JP20gm0010003 , a Grant-in-Aid for Specially Promoted Research from JSPS ( 20H05627 ), the Takeda Science Foundation , and the Mitsukoshi Health and Welfare Foundation . K.H. and M. Amagai were funded through AMED under grants 18ek0410028h0003 and 19ek0410058h0001 . We thank Seiko Narushima and Sean Kearney for technical assistance and Julia A. Segre and Heidi H. Kong for discussion. The LC-MS platform used in this study was provided by the JST ERATO Gas Biology Project, which was led by M.S. until March 2015. Funding Information: K.H. was funded through AMED LEAP under grant JP20gm0010003, a Grant-in-Aid for Specially Promoted Research from JSPS (20H05627), the Takeda Science Foundation, and the Mitsukoshi Health and Welfare Foundation. K.H. and M. Amagai were funded through AMED under grants 18ek0410028h0003 and 19ek0410058h0001. We thank Seiko Narushima and Sean Kearney for technical assistance and Julia A. Segre and Heidi H. Kong for discussion. The LC-MS platform used in this study was provided by the JST ERATO Gas Biology Project, which was led by M.S. until March 2015. K.H. and Y. Ito planned experiments, analyzed data, and wrote the manuscript, together with A.N.S.; Y. Ito, E.W. T.T. Y.L. H.H. and K.A. performed immunological analyses and bacterial cultures; Y. Ito and H. Kawasaki evaluated disease activity index of Tmem79?/? mice; T.S. and A.S. performed 16S metagenomic sequencing and maintained Tmem79?/? mice; R.K. W.S. and M.H. performed bacterial sequence analyses; Y. Ito, E.K. H. Kawasaki, and H. Koseki performed RNA-seq analysis; H. Kawasaki and M. Amagai organized skin microbiome sampling from healthy volunteers and patients with AD; H.I. and T.M. performed field emission scanning electron microscopy (FE-SEM) analysis; Y. Iwakura provided Il17a?/? mice; L.Y. J.H. and M.S. generated mutant strains of S. aureus and provided clinical isolates of S. aureus; N.O. M. Arita, Y.S. and M.S. measured steroids by LC-MS/MS; and Y.K. and O.O. performed proteomic analysis. K.H. is a scientific advisory board member of Vedanta Biosciences and 4BIO CAPITAL. Y.I. E.K. M. Amagai, and K.H. are co-inventors related to therapeutic effect of S. cohnii discussed here under patent PCT/JP2020/003957 and TW 109103376 titled ?Pharmaceutical composition for preventing, ameliorating or treating skin disease.? Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = apr,
day = "27",
doi = "10.1016/j.celrep.2021.109052",
language = "English",
volume = "35",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "4",
}
