1. T cell signaling: from development to differentiation
June 14 (TUE) 11:00 / Auditorium (1F), PBC
Linrong Lu
Zhejiang University School of Medicine
Our lab is interested in the signaling events that direct and regulate the development and/or differentiation of T cells. We have previously shown that, Tespa1, a newly-identified adaptor protein, is essential for the positive selection of thymocyte. Here we demonstrate that Tespa1 interacts with the N-terminal of type 1 inositol-1, 4, 5- triphosphate (IP3) receptor (IP3R1) and drives the recruitment of IP3R1 to the TCR complexes upon TCR stimulation. The binding of IP3R1 to Tespa1 is essential for the optimal TCR-induced Ca2+ flux. In the 2nd part of our work, we identified a new regulator of TH17 cell differentiation, MINK1 (misshapen-like kinase, which is able to inhibit SMAD2 activation through direct phosphorylation of SMAD2 at the T324 residue. Consistent with findings that MINK1 activity can be induced by reactive oxygen species (ROS), and accumulation of ROS may limit the survival and proliferation of TH17 cells, we show that the ROS scavenger N-acetyl cysteine boosts TH17 cell differentiation in a MINK1-dependent manner both in vitro and in vivo, and exacerbates the severity of EAE. Thus, we have established MINK1 as a critical regulator of TH17 cell differentiation. The contribution of MINK1 to ROS-regulated TH17 cell differentiation may suggest an important mechanism for the development of autoimmune diseases influenced by antioxidant dietary supplements.
Inquiry: Prof. Dipayan Rudra ( ) or AIM Administrative Team (Tel ,