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Type 2 innate immunity regulates hair follicle homeostasis to control Demodex pathosymbionts

View ORCID ProfileRoberto R. Ricardo-Gonzalez, View ORCID ProfileMaya E. Kotas, Iliana Tenvooren, Diana M. Marquez, View ORCID ProfileMarlys S. Fassett, Jinwoo Lee, Scott G. Daniel, Kyle Bittinger, Roberto Efraín Díaz, View ORCID ProfileJames S. Fraser, View ORCID ProfileK. Mark Ansel, View ORCID ProfileMatthew H. Spitzer, Hong-Erh Liang, View ORCID ProfileRichard M. Locksley
doi: https://doi.org/10.1101/2021.03.29.437438
Roberto R. Ricardo-Gonzalez
1Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.
2Department of Microbiology & Immunology, University of California San Francisco, San Francisco, CA, USA.
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  • ORCID record for Roberto R. Ricardo-Gonzalez
  • For correspondence: Richard.Locksley@ucsf.edu Roberto.Ricardo-Gonzalez@ucsf.edu
Maya E. Kotas
3Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
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Iliana Tenvooren
4Department of Otolaryngology and Microbiology & Immunology, University of California San Francisco, San Francisco, CA, USA.
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Diana M. Marquez
4Department of Otolaryngology and Microbiology & Immunology, University of California San Francisco, San Francisco, CA, USA.
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Marlys S. Fassett
1Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.
2Department of Microbiology & Immunology, University of California San Francisco, San Francisco, CA, USA.
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Jinwoo Lee
3Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
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Scott G. Daniel
5Division of Gastroenterology, Hepatology, and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA.
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Kyle Bittinger
5Division of Gastroenterology, Hepatology, and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA.
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Roberto Efraín Díaz
6Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
7Tetrad Graduate Program, University of California San Francisco, San Francisco, CA, USA.
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James S. Fraser
6Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
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  • ORCID record for James S. Fraser
K. Mark Ansel
2Department of Microbiology & Immunology, University of California San Francisco, San Francisco, CA, USA.
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Matthew H. Spitzer
4Department of Otolaryngology and Microbiology & Immunology, University of California San Francisco, San Francisco, CA, USA.
8Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA.
9Chan Zuckerberg Biohub, San Francisico, CA, USA.
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Hong-Erh Liang
3Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
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Richard M. Locksley
2Department of Microbiology & Immunology, University of California San Francisco, San Francisco, CA, USA.
3Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
10Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California, USA.
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  • ORCID record for Richard M. Locksley
  • For correspondence: Richard.Locksley@ucsf.edu Roberto.Ricardo-Gonzalez@ucsf.edu
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Abstract

Allergic skin diseases are common, but basal roles for type 2 immunity in cutaneous homeostasis are incompletely understood. Here, we show that skin group 2 innate lymphoid cells (ILC2s) are the predominant resident cells that secretes IL-13, which attenuates epithelial cell proliferation during anagen throughout the hair follicle (HF), including in HF stem cells. Although HF are normal in the absence of type 2 immunity, colonization with the commensal mite, Demodex musculi, results in epithelial proliferation and aberrant hair follicle morphology accompanied by loss of stable commensalism with massive infestation and expansion of inflammatory ILC2s and other immune cells. Topical anti-parasitic agents, but not broad-spectrum antibiotics, reversed the phenotype. Commensal Demodex colonization of mammalian hair follicles is ubiquitous, including in humans, revealing an unanticipated role for ILC2s and type 2 immunity for skin homeostasis in the normal environment.

One Sentence Summary Dynamic regulation of skin physiology by Type 2 innate immunity regulates healthy commensalism by parasitic Demodex mites.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted March 30, 2021.
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Type 2 innate immunity regulates hair follicle homeostasis to control Demodex pathosymbionts
Roberto R. Ricardo-Gonzalez, Maya E. Kotas, Iliana Tenvooren, Diana M. Marquez, Marlys S. Fassett, Jinwoo Lee, Scott G. Daniel, Kyle Bittinger, Roberto Efraín Díaz, James S. Fraser, K. Mark Ansel, Matthew H. Spitzer, Hong-Erh Liang, Richard M. Locksley
bioRxiv 2021.03.29.437438; doi: https://doi.org/10.1101/2021.03.29.437438
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Type 2 innate immunity regulates hair follicle homeostasis to control Demodex pathosymbionts
Roberto R. Ricardo-Gonzalez, Maya E. Kotas, Iliana Tenvooren, Diana M. Marquez, Marlys S. Fassett, Jinwoo Lee, Scott G. Daniel, Kyle Bittinger, Roberto Efraín Díaz, James S. Fraser, K. Mark Ansel, Matthew H. Spitzer, Hong-Erh Liang, Richard M. Locksley
bioRxiv 2021.03.29.437438; doi: https://doi.org/10.1101/2021.03.29.437438

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