학술논문

Commensal Microbes and Hair Follicle Morphogenesis Coordinately Drive Treg Migration into Neonatal Skin
Document Type
article
Source
Cell Host & Microbe. 21(4)
Subject
Biomedical and Clinical Sciences
Immunology
Pediatric
Clinical Research
2.1 Biological and endogenous factors
Aetiology
Skin
Animals
Chemokine CCL20
Hair Follicle
Immune Tolerance
Mice
Microbiota
Morphogenesis
Receptors
CCR6
Symbiosis
T-Lymphocytes
Regulatory
commensal-specific immune tolerance
hair follicles
migration
regulatory T cells
skin commensal microbes
tissue development
Microbiology
Medical Microbiology
Biochemistry and cell biology
Medical microbiology
Language
Abstract
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.