Commensal Microbes and Hair Follicle Morphogenesis Coordinately Drive Treg Migration into Neonatal Skin.
Regulatory T cells (Tregs) are required to establish immune tolerance to commensal microbes. Tregs accumulate abruptly in the skin during a defined window of postnatal tissue development. However, the mechanisms mediating Treg migration to neonatal skin are unknown. Here we show that hair follicle (HF) development facilitates the accumulation of Tregs in neonatal skin and that upon skin entry these cells localize to HFs, a primary reservoir for skin commensals. Further, germ-free neonates had reduced skin Tregs indicating that commensal microbes augment Treg accumulation. We identified Ccl20 as a HF-derived, microbiota-dependent chemokine and found its receptor, Ccr6, to be preferentially expressed by Tregs in neonatal skin. The Ccl20-Ccr6 pathway mediated Treg migration in vitro and in vivo. Thus, HF morphogenesis, commensal microbe colonization, and local chemokine production work in concert to recruit Tregs into neonatal skin, thereby establishing this tissue Treg niche early in life.
Department of Dermatology, University of California, San Francisco, San Francisco, CA, 94143, USA.
Tiffany C
TC
Scharschmidt
Department of Dermatology, University of California, San Francisco, San Francisco, CA, 94143, USA.
Kimberly S
KS
Vasquez
Department of Dermatology, University of California, San Francisco, San Francisco, CA, 94143, USA.
Mariela L
ML
Pauli
Department of Dermatology, University of California, San Francisco, San Francisco, CA, 94143, USA.
Elizabeth G
EG
Leitner
Department of Dermatology, University of California, San Francisco, San Francisco, CA, 94143, USA.
Kevin
K
Chu
Immuno-Oncology Group, Bristol-Meyers Squibb, Redwood City, CA, 94063, USA.
Hong-An
HA
Truong
Department of Dermatology, University of California, San Francisco, San Francisco, CA, 94143, USA.
Margaret M
MM
Lowe
Department of Dermatology, University of California, San Francisco, San Francisco, CA, 94143, USA.
Robert
R
Sanchez Rodriguez
Department of Dermatology, University of California, San Francisco, San Francisco, CA, 94143, USA.
Niwa
N
Ali
Department of Pathology, University of California, San Francisco, San Francisco, CA, 94143, USA.
Zoltan G
ZG
Laszik
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Justin L
JL
Sonnenburg
Departments of Dermatology and Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Sarah E
SE
Millar
Department of Dermatology, University of California, San Francisco, San Francisco, CA, 94143, USA. Electronic address: michael.rosenblum@ucsf.edu.
Michael D
MD
Rosenblum
D000818:Animals; D054418:Chemokine CCL20 / Q000378:metabolism; D018859:Hair Follicle / Q000254:growth & development* / Q000276:immunology / Q000382:microbiology; D007108:Immune Tolerance; D051379:Mice; D064307:Microbiota / Q000276:immunology*; D009024:Morphogenesis; D054399:Receptors, CCR6 / Q000378:metabolism; D012867:Skin / Q000276:immunology* / Q000382:microbiology*; D013559:Symbiosis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D054418:Chemokine CCL20; D054399:Receptors, CCR6
commensal-specific immune tolerance; hair follicles; migration; regulatory T cells; skin commensal microbes; tissue development