| Autor: |
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. |
| Předmět: |
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| Zdroj: |
Science Immunology; 2024, Vol. 9 Issue 91, p1-16, 16p |
| Abstrakt: |
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 (Tregs) only in skin. Selective depletion of skin Tregs 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 Tregs, functioning exclusively in a cell-extrinsic manner. In a novel model of HF stem cell (HFSC)–driven autoimmunity, we reveal that skin Tregs 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 Tregs in skin uncoupled from the systemic pool and elucidate a mechanism of self-tolerance. Editor's summary: Regulatory T cells (Tregs) are critical for maintaining peripheral tolerance, but delineation of their tissue-specific functions has been challenging because of limited availability of tools that selectively target tissue Tregs. By developing a technique to induce genetic recombination specifically in murine skin Tregs, Cohen et al. demonstrated that skin Tregs protect the hair follicle from steady-state inflammation. Suppression of hair follicle inflammation required skin Treg expression of the high-affinity interleukin-2 (IL-2) receptor but not CTLA-4. In a mouse model of T cell–mediated autoimmune attack, skin Tregs prevented destruction of hair follicle stem cells. Patients with autoimmune alopecia displayed an enhanced IL-2/STAT5 gene signature around hair follicles, indicating that dysregulation of skin Treg-mediated immunosuppression may contribute to the pathogenesis of autoimmune skin diseases. —Claire Olingy [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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