AI Article Synopsis
- The study identifies a new pair of transcription factors, Bhlhe40 and Pou2af1, that regulates CXCR5 expression, which is crucial for follicular T helper (Tfh) cell migration into germinal centers.
- Pou2af1 promotes Tfh formation and migration by increasing CXCR5 levels, while Bhlhe40 inhibits this by repressing Pou2af1 expression.
- The research suggests that the Bhlhe40-Pou2af1 regulatory circuit operates independently of the well-established Bcl6-Blimp1 circuit that traditionally governs Tfh cell fate.
Article 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.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11188140 | PMC |
| http://dx.doi.org/10.1101/2024.05.16.594397 | DOI Listing |
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