| First Author | Iwata S | Year | 2017 |
| Journal | Immunity | Volume | 46 |
| Issue | 6 | Pages | 983-991.e4 |
| PubMed ID | 28623086 | Mgi Jnum | J:259235 |
| Mgi Id | MGI:6142817 | Doi | 10.1016/j.immuni.2017.05.005 |
| Citation | Iwata S, et al. (2017) The Transcription Factor T-bet Limits Amplification of Type I IFN Transcriptome and Circuitry in T Helper 1 Cells. Immunity 46(6):983-991.e4 |
| abstractText | Host defense requires the specification of CD4(+) helper T (Th) cells into distinct fates, including Th1 cells that preferentially produce interferon-gamma (IFN-gamma). IFN-gamma, a member of a large family of anti-pathogenic and anti-tumor IFNs, induces T-bet, a lineage-defining transcription factor for Th1 cells, which in turn supports IFN-gamma production in a feed-forward manner. Herein, we show that a cell-intrinsic role of T-bet influences how T cells perceive their secreted product in the environment. In the absence of T-bet, IFN-gamma aberrantly induced a type I IFN transcriptomic program. T-bet preferentially repressed genes and pathways ordinarily activated by type I IFNs to ensure that its transcriptional response did not evoke an aberrant amplification of type I IFN signaling circuitry, otherwise triggered by its own product. Thus, in addition to promoting Th1 effector commitment, T-bet acts as a repressor in differentiated Th1 cells to prevent abberant autocrine type I IFN and downstream signaling. |
