| Autor: |
Sato, Yuki, Jain, Abhinav, Ohtsuki, Shozo, Okuyama, Hirohisa, Sturmlechner, Ines, Takashima, Yoshinori, Le, Kevin-Phu C., Bois, Melanie C., Berry, Gerald J., Warrington, Kenneth J., Goronzy, Jörg J., Weyand, Cornelia M. |
| Předmět: |
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| Zdroj: |
Science Translational Medicine; 9/6/2023, Vol. 15 Issue 712, p1-18, 18p |
| Abstrakt: |
Autoimmune vasculitis of the medium and large elastic arteries can cause blindness, stroke, aortic arch syndrome, and aortic aneurysm. The disease is often refractory to immunosuppressive therapy and progresses over decades as smoldering aortitis. How the granulomatous infiltrates in the vessel wall are maintained and how tissue-infiltrating T cells and macrophages are replenished are unknown. Single-cell and whole-tissue transcriptomic studies of immune cell populations in vasculitic arteries identified a CD4+ T cell population with stem cell–like features. CD4+ T cells supplying the tissue-infiltrating and tissue-damaging effector T cells survived in tertiary lymphoid structures around adventitial vasa vasora, expressed the transcription factor T cell factor 1 (TCF1), had high proliferative potential, and gave rise to two effector populations, Eomesodermin (EOMES)+ cytotoxic T cells and B cell lymphoma 6 (BCL6)+ T follicular helper-like cells. TCF1hiCD4+ T cells expressing the interleukin 7 receptor (IL-7R) sustained vasculitis in serial transplantation experiments. Thus, TCF1hiCD4+ T cells function as disease stem cells and promote chronicity and autonomy of autoimmune tissue inflammation. Remission-inducing therapies will require targeting stem-like CD4+ T cells instead of only effector T cells. Editor's summary: Giant cell arteritis (GCA) is an autoimmune disease of the medium and large arteries that affects older adults and is often refractory to standard immunosuppression. Although T cell infiltrates occupy the vessel walls in patients with GCA, the source of these cells, and their importance in driving disease, is unclear. Here, Sato et al. found, using both human aortic tissues and serial transplantation experiments in mice, that a population of stem-like CD4+ T cells residing in tertiary lymphoid structures replenishes pathogenic effector cells independent of secondary lymphoid organs. Targeting such stem-like CD4+ T cells may represent a therapeutic opportunity to halt the chronic progression of autoimmune vasculitis. —Courtney Malo [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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