Lagarrigue Frederic, Gertler Frank B, Ginsberg Mark H, Cantor Joseph M
Department of Medicine, University of California San Diego, La Jolla, CA 92093; and.
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142.
J Immunol. 2017 May 1;198(9):3410-3415. doi: 10.4049/jimmunol.1601743. Epub 2017 Mar 27.
Rap1-interacting adaptor molecule (RIAM) is a Rap1 effector that mediates the recruitment of talin to integrins, thereby supporting their activation. In this study, we investigated the role of RIAM in an adoptive transfer model for type I diabetes and report that RIAM expression in T cells is necessary for diabetes development. Loss of RIAM did not prevent lymphocyte recruitment to draining lymph nodes 24 h after transfer, but it was required for Ag-driven proliferation and cytotoxic killing. RIAM is recruited to immune synapses along with talin and LFA-1, and loss of RIAM profoundly suppresses Ag-dependent conjugate formation in primary naive and effector T cells. These data identify the requirement of RIAM for formation of immunological synapses and in resulting T cell functions in autoimmunity. Moreover, because RIAM-null mice are healthy, fertile, and display no bleeding abnormalities, our results identify RIAM and its regulators as potential targets for therapies of T cell-mediated autoimmunity.
Rap1相互作用衔接分子（RIAM）是一种Rap1效应蛋白，介导踝蛋白募集至整合素，从而支持整合素的激活。在本研究中，我们在I型糖尿病的过继转移模型中研究了RIAM的作用，并报告T细胞中RIAM的表达是糖尿病发展所必需的。RIAM缺失并不妨碍转移后24小时淋巴细胞募集至引流淋巴结，但抗原驱动的增殖和细胞毒性杀伤需要RIAM。RIAM与踝蛋白和淋巴细胞功能相关抗原-1（LFA-1）一起被募集至免疫突触，RIAM缺失会显著抑制原代幼稚和效应T细胞中抗原依赖性共轭形成。这些数据确定了RIAM在自身免疫中形成免疫突触及由此产生的T细胞功能方面的必要性。此外，由于RIAM基因敲除小鼠健康、可育且无出血异常，我们的结果确定RIAM及其调节因子是T细胞介导的自身免疫治疗的潜在靶点。
