期刊
CELL REPORTS
卷 29, 期 7, 页码 1848-+出版社
CELL PRESS
DOI: 10.1016/j.celrep.2019.10.012
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资金
- NIH [AI48125/AI37562]
- LeRoy Schecter Research Foundation
- National Natural Science Foundation of China [81971482]
- Sahlgrenska Academy
- University of Gothenburg
- Foundation Blanceflor Boncompagni Ludovisi
- University of Alabama at Birmingham
Follicular regulatory T (T-FR) cells are a specialized suppressive subset that controls the germinal center (GC) response and maintains humoral self-tolerance. The mechanisms that maintain TFR lineage identity and suppressive activity remain largely unknown. Here, we show that expression of Blimp1 by FoxP3(+) T-FR cells is essential for TFR lineage stability, entry into the GC, and expression of regulatory activity. Deletion of Blimp1 in T-FR cells reduced FoxP3 and CTLA-4 expression and increased pro-inflammatory cytokines and spontaneous production of autoanti-bodies, including elevated IgE. Maintenance of T-FR stability reflected Blimp1-dependent repression of the IL-23R-STAT3 axis and activation of the CD25-STAT5 pathway, while silenced IL-23R-STAT3 or increased STAT5 activation rescued the Blimp1-deficient T-FR phenotype. Blimp1-dependent control of CXCR5/CCR7 expression also regulated T-FR homing into the GC. These findings uncover a Blimp1-dependent T-FR checkpoint that enforces suppressive activity and acts as a gatekeeper of GC entry.
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