Journal
IMMUNITY
Volume 46, Issue 6, Pages 983-+Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2017.05.005
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Funding
- Intramural Research Program of NIAMS
- Intramural Research Program of NIAID
- Grants-in-Aid for Scientific Research [26221305, 15K08522, 17K08876] Funding Source: KAKEN
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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 antipathogenic 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 cellintrinsic 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.
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