Other
14 Authors
- Wen R,
- Podd A,
- Qi X,
- Chen Y,
- Li HS,
- Watowich SS,
- Qi H,
- Huang H,
- Wang J,
- Yu M,
- Nurieva RI,
- Wang D,
- Dong C,
- Alekseev AM
| First Author | Nurieva RI | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 14 | Pages | 11234-9 |
| PubMed ID | 22318729 | Mgi Jnum | J:244647 |
| Mgi Id | MGI:5913426 | Doi | 10.1074/jbc.M111.324046 |
| Citation | Nurieva RI, et al. (2012) STAT5 protein negatively regulates T follicular helper (Tfh) cell generation and function. J Biol Chem 287(14):11234-9 |
| abstractText | Recent work has identified a new subset of CD4(+) T cells named as Tfh cells that are localized in germinal centers and critical in germinal center formation. Tfh cell differentiation is regulated by IL-6 and IL-21, possibly via STAT3 factor, and B cell lymphoma 6 (Bcl6) is specifically expressed in Tfh cells and required for their lineage specification. In the current study, we characterized the role of STAT5 in Tfh cell development. We found that a constitutively active form of STAT5 effectively inhibited Tfh differentiation by suppressing the expression of Tfh-associated factors (CXC motif) receptor 5 (CXCR5), musculoaponeurotic fibrosarcoma (c-Maf), Bcl6, basic leucine zipper transcription factor ATF-like (Batf), and IL-21, and STAT5 deficiency greatly enhanced Tfh gene expression. Importantly, STAT5 regulated the expression of Tfh cell suppressor factor B lymphocyte-induced maturation protein 1 (Blimp-1); STAT5 deficiency impaired Blimp-1 expression and resulted in elevated expression of Tfh-specific genes. Similarly, inhibition of IL-2 potentiated Tfh generation, associated with dampened Blimp-1 expression; Blimp-1 overexpression inhibited Tfh gene expression in Stat5-deficient T cells, suggesting that the IL-2/STAT5 axis functions to regulate Blimp-1 expression. In vivo, deletion of STAT5 in CD4(+) T cells resulted in enhanced development of Tfh cells and germinal center B cells and led to an impairment of B cell tolerance in a well defined mouse tolerance model. Taken together, this study demonstrates that STAT5 controls Tfh differentiation. |
