T-bet, a Th1 transcription factor regulates the expression of Tim-3

T‐cell immunoglobulin, mucin domain‐3 (Tim‐3) is a membrane protein expressed at late stages of IFN‐γ secreting CD4+ Th1 cell differentiation and constitutively on DC. Ligation of Tim‐3 on Th1 cells terminates Th1 immune responses. In addition, Tim‐3 plays a role in tolerance induction, although the mechanism by which this is accomplished has yet to be elucidated. While it is clear that Tim‐3 plays an important role in the immune system, little is known regarding the molecular pathways that regulate Tim‐3 expression. In the current study, we examine the role of Th1‐associated transcription factors in regulating Tim‐3 expression. Our experiments reveal that Tim‐3 expression is regulated by the Th1‐specific transcription factor T‐bet. This introduces a novel paradigm into the generation of a Th1 response, whereby a transcription factor responsible for effector Th1 cell differentiation also increases the expression of a specific counter‐regulatory molecule to ensure appropriate termination of pro‐inflammatory Th1 immune responses.