Optimal CXCR5 expression during Tfh maturation involves the Bhlhe40-Pou2af1 axis

作者：Xiaoliang Zhu, Xi Chen, Yaqiang Cao, Chengyu Liu, Zoey J Kline, Gangqing Hu, Sundar Ganesan, Tibor Z. Veres, Difeng Fang, Shuai Liu, Danping Wei, Hirofumi Shibata, Dominic P. Golec, Hyunwoo Chung, Ronald N. Germain, Pamela L. Schwartzberg, Keji Zhao, Jinfang Zhu · 发表于：Cell Reports · 年份：2025 · DOI：10.1016/j.celrep.2025.116470 · 被引用次数：4 · 研究领域：interferon and immune responses、Chemokine receptors and signaling、Cytokine Signaling Pathways and Interactions

The pair of transcription factors Bcl6-Blimp1 is well known for follicular T helper (Tfh) early cell fate determination; however, the mechanism(s) for late regulation of CXCR5 during Tfh migration into germinal centers (GCs) is still unclear. In this study, we uncovered another pair of transcription factors, Bhlhe40-Pou2af1, that regulate CXCR5 expression. Pou2af1 was specifically expressed in Tfh cells, whereas Bhlhe40 expression was found to be high in non-Tfh cells. Pou2af1 promoted Tfh formation and migration into a GC by upregulating CXCR5 but not Bcl6, while Bhlhe40 repressed this process by inhibiting Pou2af1 expression. RNA sequencing analysis of antigen-specific Tfh cells generated in vivo confirmed the role of Bhlhe40-Pou2af1 axis in regulating optimal CXCR5 expression. Thus, the regulation of CXCR5 expression and migration of Tfh cells into a GC involves a transcriptional regulatory circuit consisting of Bhlhe40 and Pou2af1, which does not affect the Bcl6-Blimp1 circuit that determines the Tfh cell fate.