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

• Published in: Science immunology Vol. 9; no. 91; p. eadh0152
• Main Authors: Cohen, Jarish N, Gouirand, Victoire, Macon, Courtney E, Lowe, Margaret M, Boothby, Ian C, Moreau, Joshua M, Gratz, Iris K, Stoecklinger, Angelika, Weaver, Casey T, Sharpe, Arlene H, Ricardo-Gonzalez, Roberto R, Rosenblum, Michael D
• Format: Journal Article
• Language: English
• Published: United States 05.01.2024
• Subjects: Hair Follicle; Humans; Immune Privilege; Interleukin-2; Stem Cell Niche; T-Lymphocytes, Regulatory
• ISSN: 2470-9468
• DOI: 10.1126/sciimmunol.adh0152

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 ) only in skin. Selective depletion of skin T 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 , functioning exclusively in a cell-extrinsic manner. In a novel model of HF stem cell (HFSC)-driven autoimmunity, we reveal that skin T 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 in skin uncoupled from the systemic pool and elucidate a mechanism of self-tolerance.