Regulatory T cells in skin mediate immune privilege of the hair follicle stem cell niche

Jarish N Cohen; Victoire Gouirand; Courtney E Macon; Margaret M Lowe; Ian C Boothby; Joshua M Moreau; Iris K Gratz; Angelika Stoecklinger; Casey T Weaver; Arlene H Sharpe; Roberto R Ricardo-Gonzalez; Michael D Rosenblum

doi:10.1126/sciimmunol.adh0152

Regulatory T cells in skin mediate immune privilege of the hair follicle stem cell niche

Sci Immunol. 2024 Jan 5;9(91):eadh0152. doi: 10.1126/sciimmunol.adh0152. Epub 2024 Jan 5.

Authors

Jarish N Cohen^{1

2}, Victoire Gouirand¹, Courtney E Macon¹, Margaret M Lowe¹, Ian C Boothby^{1

3}, Joshua M Moreau^{4

5

6}, Iris K Gratz⁷, Angelika Stoecklinger^{7

8}, Casey T Weaver⁹, Arlene H Sharpe^{10

11

12}, Roberto R Ricardo-Gonzalez¹, Michael D Rosenblum¹

Affiliations

¹ Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA.
² Department of Pathology, University of California, San Francisco, San Francisco, CA, USA.
³ Medical Scientist Training Program, University of California, San Francisco, CA, USA.
⁴ Department of Cell, Developmental, and Cancer Biology, Oregon Health Sciences University, Portland, OR, USA.
⁵ Department of Dermatology, Oregon Health Sciences University, Portland, OR, USA.
⁶ Department of Oncological Sciences, Oregon Health Sciences University, Portland, OR, USA.
⁷ Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
⁸ EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology, University Hospital of the Paracelsus Medical, University of Salzburg, Salzburg, Austria.
⁹ Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
¹⁰ Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
¹¹ Evergrande Center for Immunological Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
¹² Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.

Abstract

Immune tolerance is maintained in lymphoid organs (LOs). Despite the presence of complex immune cell networks in non-LOs, it is unknown whether self-tolerance is maintained in these tissues. We developed a technique to restrict genetic recombination to regulatory T cells (T_regs) only in skin. Selective depletion of skin T_regs resulted in T cell-mediated inflammation of hair follicles (HFs). Suppression did not rely on CTLA-4, but instead on high-affinity interleukin-2 (IL-2) receptor expression by skin T_regs, functioning exclusively in a cell-extrinsic manner. In a novel model of HF stem cell (HFSC)-driven autoimmunity, we reveal that skin T_regs immunologically protect the HFSC niche. Finally, we used spatial transcriptomics to identify aberrant IL-2 signaling at stromal-HF interfaces in a rare form of human alopecia characterized by HFSC destruction and alopecia areata. Collectively, these results reveal the fundamental biology of T_regs in skin uncoupled from the systemic pool and elucidate a mechanism of self-tolerance.

MeSH terms

Hair Follicle
Humans
Immune Privilege*
Interleukin-2
Stem Cell Niche
T-Lymphocytes, Regulatory*

Substances

Interleukin-2

Abstract

MeSH terms

Substances

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