Cell ReportsImmunologyPeer-reviewed journal article
Optimal CXCR5 Expression during Tfh Maturation Involves the Bhlhe40-Pou2af1 Axis
Xiaoliang Zhu, Xi CheniD, Yaqiang CaoiD, Chengyu LiuiD, Zoey J. KlineiD, Gangqing HuiD, Sundar GanesaniD, Tibor Z. VeresiD, Difeng FangiD, Shuai LiuiD, Danping WeiiD, Hirofumi ShibataiD, Dominic P. GoleciD, Hyunwoo Chung, Ronald N. GermainiD, Pamela L. SchwartzbergiD, Keji ZhaoiD, Jinfang ZhuiD
Abstract
The pair of transcription factors Bcl6-Blimp1 is well-known for follicular T helper (Tfh) cell fate determination, however, the mechanism(s) for Bcl6-independent regulation of CXCR5 during Tfh migration into germinal center (GC) is still unclear. In this study, we uncovered another pair of transcription factors, Bhlhe40-Pou2af1, that regulates CXCR5 expression. Pou2af1 was specifically expressed in Tfh cells whereas Bhlhe40 expression was found high in non-Tfh cells. Pou2af1 promoted Tfh formation and migration into GC by upregulating CXCR5 but not Bcl6, while Bhlhe40 repressed this process by inhibiting Pou2af1 expression. RNA-Seq 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 GC involves a transcriptional regulatory circuit consisting of Bhlhe40 and Pou2af1, which operates independent of the Bcl6-Blimp1 circuit that determines the Tfh cell fate.
- organism: mouse
- assay: bulk RNA-seq
- research focus: cell type annotation
- research focus: differential expression
- approach: statistical model
- Citations
- 8
- FWCI
- 2.60
- Field percentile
- top 9%
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