@article{7588f128a9124eb0936d3bdf9f3bacbe,
title = "Bacteria induce skin regeneration via IL-1β signaling",
abstract = "Environmental factors that enhance regeneration are largely unknown. The immune system and microbiome are attributed roles in repairing and regenerating structure but their precise interplay is unclear. Here, we assessed the function of skin bacteria in wound healing and wound-induced hair follicle neogenesis (WIHN), a rare adult organogenesis model. WIHN levels and stem cell markers correlate with bacterial counts, being lowest in germ-free (GF), intermediate in conventional specific pathogen-free (SPF), and highest in wild-type mice, even those infected with pathogenic Staphylococcus aureus. Reducing skin microbiota via cage changes or topical antibiotics decreased WIHN. Inflammatory cytokine IL-1β and keratinocyte-dependent IL-1R-MyD88 signaling are necessary and sufficient for bacteria to promote regeneration. Finally, in a small trial, a topical broad-spectrum antibiotic also slowed skin wound healing in adult volunteers. These results demonstrate a role for IL-1β to control morphogenesis and support the need to reconsider routine applications of topical prophylactic antibiotics.",
keywords = "bacteria, hair, regeneration",
author = "Gaofeng Wang and Evan Sweren and Haiyun Liu and Eric Wier and Alphonse, {Martin P.} and Ruosi Chen and Nasif Islam and Ang Li and Yingchao Xue and Junjie Chen and Seungman Park and Yun Chen and Sam Lee and Yu Wang and Saifeng Wang and Archer, {Nate K.} and William Andrews and Kane, {Maureen A.} and Erika Dare and Reddy, {Sashank K.} and Zhiqi Hu and Grice, {Elizabeth A.} and Miller, {Lloyd S.} and Garza, {Luis A.}",
note = "Funding Information: The authors thank the Cutaneous Translational Research Program (CTReP) at the Department of Dermatology for organizing human subjects and preparing tissue samples. Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases , part of the National Institutes of Health , under R01AR074846 01 to LAG. This work was also supported by the Northrop Grumman Electronic Systems as well as the Thomas Provost, MD Young Faculty Development Fund of Johns Hopkins Dermatology to LAG. Funding Information: The authors thank the Cutaneous Translational Research Program (CTReP) at the Department of Dermatology for organizing human subjects and preparing tissue samples. Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, part of the National Institutes of Health, under R01AR074846 01 to LAG. This work was also supported by the Northrop Grumman Electronic Systems as well as the Thomas Provost, MD Young Faculty Development Fund of Johns Hopkins Dermatology to LAG. G.W. H.L. and L.A.G. designed the study and experiments; G.W. E.S. and L.A.G. wrote the manuscript; G.W. performed the experiments and analyzed the data; H.L. E.S. E.W. M.A. N.I. A.I. Y.X. R.C. J.C. Y.C. S.L. Y.W. N.A. A.W. K.M. E.D. Z.H. E.G. L.M. and L.A.G. participated in performing experiments, provided intellectual expertise, and/or helped to interpret experimental results; G.W. assisted with microarray and RNA-seq data analysis and isolated and cultured keratinocytes. G.W. and H.L. performed confocal microscopy and bacteria culture; G.W. and E.S. analyzed human skin biopsies; G.W. analyzed the 16S rRNA data and performed wounding studies and GF experiments. L.S.M. is a full-time employee of Janssen Pharmaceuticals and may hold Johnson & Johnson stock and stock options. L.S.M. performed all work at his prior affiliation at Johns Hopkins University School of Medicine, and he has received prior grant support from Astra Zeneca, Pfizer, Boehringer Ingelheim, Regeneron Pharmaceuticals, and Moderna Therapeutics; he was also a paid consultant for Armirall and Janssen Research and Development, was on the scientific advisory board of Integrated Biotherapeutics, and is a shareholder of Noveome Biotherapeutics, which are all developing therapeutics against infections (including S. aureus and other pathogens) and/or inflammatory conditions. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = may,
day = "12",
doi = "10.1016/j.chom.2021.03.003",
language = "English (US)",
volume = "29",
pages = "777--791.e6",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "5",
}