Transcriptional Regulation of the Inducible Costimulator (ICOS) in T Cells

The inducible costimulator (ICOS) is a member of the CD28 family of costimulatory molecules and plays a central role in T-cell-mediated immunity. In this study, we investigated the molecular regulation of ICOS expression during early activation of CD4+ T cells by T cell receptor and CD28 co-engagement as well as during the differentiation of these cells into Th1 and Th2 lineages. In recently activated T cells, our data suggests that the Fyn-calcineurin-NFATc2 and MEK2-ERK1/2 signaling axes cooperate to transactivate icos transcription by acting on two different sites of its promoter. In T cells undergoing differentiation, we found that T-bet in Th1 or GATA-3 in Th2 cells could enhance, and NFATc2 could further synergize with either of them to increase, icos transcription via the icos promoter or a 3o "UTR element respectively. Finally, we also found that ICOS is controlled at a post-transcriptional level by the RING-type E3 ubiquitin ligase, roquin.

Author dc:creator

• TAN HEE MENG ANDY

• inducible costimulator, T cell, T-bet, GATA-3, NFATc2, Th differentiation