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Cell. 2017 Jun 1;169(6):1119-1129.e11. doi: 10.1016/j.cell.2017.05.002. Epub 2017 May 25.

Regulatory T Cells in Skin Facilitate Epithelial Stem Cell Differentiation.

Author information

1
Department of Dermatology, University of California, San Francisco, San Francisco, CA 94143, USA; Cutaneous Medicine Unit, St. John's Institute of Dermatology, King's College London, London WC2R 2LS, UK.
2
Department of Dermatology, University of California, San Francisco, San Francisco, CA 94143, USA.
3
Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
4
Department of Dermatology, University of Muenster, 48149 Muenster, Germany.
5
Cutaneous Medicine Unit, St. John's Institute of Dermatology, King's College London, London WC2R 2LS, UK.
6
Centre for Dermatological Research, University of Manchester & NIHR Manchester Biomedical Research Centre, Manchester M13 9PL, UK.
7
Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
8
Department of Dermatology, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: michael.rosenblum@ucsf.edu.

Abstract

The maintenance of tissue homeostasis is critically dependent on the function of tissue-resident immune cells and the differentiation capacity of tissue-resident stem cells (SCs). How immune cells influence the function of SCs is largely unknown. Regulatory T cells (Tregs) in skin preferentially localize to hair follicles (HFs), which house a major subset of skin SCs (HFSCs). Here, we mechanistically dissect the role of Tregs in HF and HFSC biology. Lineage-specific cell depletion revealed that Tregs promote HF regeneration by augmenting HFSC proliferation and differentiation. Transcriptional and phenotypic profiling of Tregs and HFSCs revealed that skin-resident Tregs preferentially express high levels of the Notch ligand family member, Jagged 1 (Jag1). Expression of Jag1 on Tregs facilitated HFSC function and efficient HF regeneration. Taken together, our work demonstrates that Tregs in skin play a major role in HF biology by promoting the function of HFSCs.

KEYWORDS:

Jagged 1; Notch; alopecia areata; hair; hair follicle stem cell; hair regeneration; regulatory T cell; skin

PMID:
28552347
PMCID:
PMC5504703
DOI:
10.1016/j.cell.2017.05.002
[Indexed for MEDLINE]
Free PMC Article

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