Regulatory T cells in skin mediate immune privilege of the hair follicle stem cell niche-Reference-Cited by-同舟云学术

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

Published:2024-01-12 Issue:91 Volume:9 Page:
ISSN:2470-9468
Container-title:Science Immunology
language:en
Short-container-title:Sci. Immunol.

Author:

Cohen Jarish N.¹²^ORCID,Gouirand Victoire¹^ORCID,Macon Courtney E.¹^ORCID,Lowe Margaret M.¹^ORCID,Boothby Ian C.¹³^ORCID,Moreau Joshua M.⁴⁵⁶^ORCID,Gratz Iris K.⁷^ORCID,Stoecklinger Angelika⁷⁸^ORCID,Weaver Casey T.⁹^ORCID,Sharpe Arlene H.¹⁰¹¹¹²^ORCID,Ricardo-Gonzalez Roberto R.¹^ORCID,Rosenblum Michael D.¹^ORCID

Affiliation:

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine,Immunology

Link

https://www.science.org/doi/pdf/10.1126/sciimmunol.adh0152

Reference63 articles.

1. A CENTRAL ROLE FOR CENTRAL TOLERANCE

2. Projection of an Immunological Self Shadow Within the Thymus by the Aire Protein

3. Central tolerance: good but imperfect

4. Mechanisms maintaining peripheral tolerance

5. Lymph node stromal cells: cartographers of the immune system