Innate type 2 immunity controls hair follicle commensalism by Demodex mites.

Autor:	Ricardo-Gonzalez RR; Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA; Department of Microbiology & Immunology, University of California, San Francisco, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA. Electronic address: roberto.ricardo-gonzalez@ucsf.edu., Kotas ME; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA., O'Leary CE; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA., Singh K; Department of Dermatology, Yale School of Medicine, New Haven, CT, USA., Damsky W; Department of Dermatology, Yale School of Medicine, New Haven, CT, USA; Department of Pathology, Yale School of Medicine, New Haven, CT, USA., Liao C; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA., Arouge E; Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA., Tenvooren I; Department of Otolaryngology and Microbiology & Immunology, University of California, San Francisco, San Francisco, CA, USA., Marquez DM; Department of Otolaryngology and Microbiology & Immunology, University of California, San Francisco, San Francisco, CA, USA., Schroeder AW; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA., Cohen JN; Department of Pathology, University of California, San Francisco, San Francisco, CA, USA., Fassett MS; Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA; Department of Microbiology & Immunology, University of California, San Francisco, San Francisco, CA, USA., Lee J; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA., Daniel SG; Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA, USA., Bittinger K; Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA, USA., Díaz RE; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA; Tetrad Graduate Program, University of California, San Francisco, San Francisco, CA, USA., Fraser JS; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA., Ali N; Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA., Ansel KM; Department of Microbiology & Immunology, University of California, San Francisco, San Francisco, CA, USA., Spitzer MH; Department of Otolaryngology and Microbiology & Immunology, University of California, San Francisco, San Francisco, CA, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA., Liang HE; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA., Locksley RM; Department of Microbiology & Immunology, University of California, San Francisco, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA, USA. Electronic address: richard.locksley@ucsf.edu.
Jazyk:	angličtina
Zdroj:	Immunity [Immunity] 2022 Oct 11; Vol. 55 (10), pp. 1891-1908.e12. Date of Electronic Publication: 2022 Aug 30.
DOI:	10.1016/j.immuni.2022.08.001
Abstrakt:	Demodex mites are commensal parasites of hair follicles (HFs). Normally asymptomatic, inflammatory outgrowth of mites can accompany malnutrition, immune dysfunction, and aging, but mechanisms restricting Demodex outgrowth are not defined. Here, we show that control of mite HF colonization in mice required group 2 innate lymphoid cells (ILC2s), interleukin-13 (IL-13), and its receptor, IL-4Ra-IL-13Ra1. HF-associated ILC2s elaborated IL-13 that attenuated HFs and epithelial proliferation at anagen onset; in their absence, Demodex colonization led to increased epithelial proliferation and replacement of gene programs for repair by aberrant inflammation, leading to the loss of barrier function and HF exhaustion. Humans with rhinophymatous acne rosacea, an inflammatory condition associated with Demodex, had increased HF inflammation with decreased type 2 cytokines, consistent with the inverse relationship seen in mice. Our studies uncover a key role for skin ILC2s and IL-13, which comprise an immune checkpoint that sustains cutaneous integrity and restricts pathologic infestation by colonizing HF mites. Competing Interests: Declaration of interests R.M.L. is a member of the Scientific Resource Board at Genentech and serves on the Advisory Board at Immunity. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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