title: Cutting Edge: Loss of T Cell RIAM Precludes Conjugate Formation with APC and Prevents Immune-Mediated Diabetes.
abstract: 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.
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA 92093; and.
authors.forename: Frederic
authors.initials: F
authors.lastname: Lagarrigue
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142.
authors.forename: Frank B
authors.initials: FB
authors.lastname: Gertler
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA 92093; and.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Ginsberg
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA 92093; and jmcantor@ucsd.edu.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Cantor
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D006801:Humans; D054992:Immunological Synapses / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D016608:Talin / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016169:Lymphocyte Function-Associated Antigen-1; D008565:Membrane Proteins; C521189:RIAM protein, mouse; D016608:Talin