| First Author | Cohen JN | Year | 2024 |
| Journal | Sci Immunol | Volume | 9 |
| Issue | 91 | Pages | eadh0152 |
| PubMed ID | 38181095 | Mgi Jnum | J:344206 |
| Mgi Id | MGI:7572639 | Doi | 10.1126/sciimmunol.adh0152 |
| Citation | Cohen JN, et al. (2024) Regulatory T cells in skin mediate immune privilege of the hair follicle stem cell niche. Sci Immunol 9(91):eadh0152 |
| abstractText | 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. |