| First Author | Fang D | Year | 2018 |
| Journal | J Exp Med | Volume | 215 |
| Issue | 11 | Pages | 2705-2714 |
| PubMed ID | 30232200 | Mgi Jnum | J:268992 |
| Mgi Id | MGI:6272899 | Doi | 10.1084/jem.20180927 |
| Citation | Fang D, et al. (2018) Transient T-bet expression functionally specifies a distinct T follicular helper subset. J Exp Med 215(11):2705-2714 |
| abstractText | T follicular helper (Tfh) cells express transcription factor BCL-6 and cytokine IL-21. Mature Tfh cells are also capable of producing IFN-gamma without expressing the Th1 transcription factor T-bet. Whether this IFN-gamma-producing Tfh population represents a unique Tfh subset with a distinct differentiation pathway is poorly understood. By using T-bet fate-mapping mouse strains, we discovered that almost all the IFN-gamma-producing Tfh cells have previously expressed T-bet and express high levels of NKG2D. DNase I hypersensitivity analysis indicated that the Ifng gene locus is partially accessible in this "ex-T-bet" population with a history of T-bet expression. Furthermore, multicolor tissue imaging revealed that the ex-T-bet Tfh cells found in germinal centers express IFN-gamma in situ. Finally, we found that IFN-gamma-expressing Tfh cells are absent in T-bet-deficient mice, but fully present in mice with T-bet deletion at late stages of T cell differentiation. Together, our findings demonstrate that transient expression of T-bet epigenetically imprints the Ifng locus for cytokine production in this Th1-like Tfh cell subset. |
