IQGAP1 regulates OX40 costimulatory signaling in CD4+ T cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K19123
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Tohoku University
• Principal Investigator: Okuyama Yuko 東北大学, 医学系研究科, 助教 (50624475)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: T細胞補助刺激 / OX40 / 自己免疫疾患

Outline of Final Research Achievements

We have discovered that OX40 associated with a scaffold protein IQGAP1 after ligation by OX40L　expressed on antigen-presenting cells. The C-terminal domain of IQGAP1 (IQGAP1-C) was required for its association with OX40, and TRAF2 augmented the binding between OX40 and IQGAP1-C. Naive CD4+ T cells from Iqgap1-/- mice displayed an enhanced ability to produce effector cytokines in response to antigen and OX40L. Retroviral transduction of IQGAP1-C into Iqgap1-/- T cells rescued these enhanced responses, suggesting that IQGAP1 limits the process of OX40-dependent T cell activation. Sublethally irradiated recipient mice that received adoptively transferred Iqgap1-/- CD4+ T cells and were immunized with MOG peptide had significantly higher EAE clinical scores than those recipient mice with wild-type CD4+ T cells. These results demonstrate that IQGAP1 is a component of the OX40 signalosome and limits cosignaling that promotes T cell activation and autoimmune disease development.

Free Research Field

免疫学