TY - JOUR
T1 - Stem-like CD4+ T cells in perivascular tertiary lymphoid structures sustain autoimmune vasculitis
AU - Sato, Yuki
AU - Jain, Abhinav
AU - Ohtsuki, Shozo
AU - Okuyama, Hirohisa
AU - Sturmlechner, Ines
AU - Takashima, Yoshinori
AU - Le, Kevin Phu C.
AU - Bois, Melanie C.
AU - Berry, Gerald J.
AU - Warrington, Kenneth J.
AU - Goronzy, Jörg J.
AU - Weyand, Cornelia M.
N1 - Publisher Copyright:
Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
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U2 - 10.1126/SCITRANSLMED.ADH0380
DO - 10.1126/SCITRANSLMED.ADH0380
M3 - Article
C2 - 37672564
AN - SCOPUS:85169998446
SN - 1946-6234
VL - 15
JO - Science translational medicine
JF - Science translational medicine
IS - 712
M1 - eadh0380
ER -