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Control of Germinal Center Localization and Lineage Stability of Follicular Regulatory T Cells by the Blimp1 Transcription Factor.


ABSTRACT: Follicular regulatory T (TFR) 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+ TFR cells is essential for TFR lineage stability, entry into the GC, and expression of regulatory activity. Deletion of Blimp1 in TFR cells reduced FoxP3 and CTLA-4 expression and increased pro-inflammatory cytokines and spontaneous production of autoantibodies, including elevated IgE. Maintenance of TFR 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 TFR phenotype. Blimp1-dependent control of CXCR5/CCR7 expression also regulated TFR homing into the GC. These findings uncover a Blimp1-dependent TFR checkpoint that enforces suppressive activity and acts as a gatekeeper of GC entry.

SUBMITTER: Shen E 

PROVIDER: S-EPMC6897316 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Control of Germinal Center Localization and Lineage Stability of Follicular Regulatory T Cells by the Blimp1 Transcription Factor.

Shen Erxia E   Rabe Hardis H   Luo Lin L   Wang Lei L   Wang Qin Q   Yin Jie J   Yang Xueying X   Liu Wenquan W   Sido Jessica M JM   Nakagawa Hidetoshi H   Ao Lin L   Kim Hye-Jung HJ   Cantor Harvey H   Leavenworth Jianmei W JW  

Cell reports 20191101 7


Follicular regulatory T (T<sub>FR</sub>) cells are a specialized suppressive subset that controls the germinal center (GC) response and maintains humoral self-tolerance. The mechanisms that maintain T<sub>FR</sub> lineage identity and suppressive activity remain largely unknown. Here, we show that expression of Blimp1 by FoxP3<sup>+</sup> T<sub>FR</sub> cells is essential for T<sub>FR</sub> lineage stability, entry into the GC, and expression of regulatory activity. Deletion of Blimp1 in T<sub>F  ...[more]

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