Integrin activation mediates lymphocyte trafficking and immune functions. Conventional T cell (Tconv cell) integrin activation requires Rap1-interacting adaptor molecule (RIAM). Here, we report that Apbb1ip−/− (RIAM-null) mice are protected from spontaneous colitis due to IL-10 deficiency, a model of inflammatory bowel disease (IBD). Protection is ascribable to reduced accumulation and homing of Tconv cells in gut-associated lymphoid tissue (GALT). Surprisingly, there are abundant RIAM-null regulatory T cells (T reg cells) in the GALT. RIAM-null T reg cells exhibit normal homing to GALT and lymph nodes due to preserved activation of integrins αLβ2, α4β1, and α4β7. Similar to Tconv cells, T reg cell integrin activation and immune function require Rap1; however, lamellipodin (Raph1), a RIAM paralogue, compensates for RIAM deficiency. Thus, in contrast to Tconv cells, RIAM is dispensable for T reg cell integrin activation and suppressive function. In consequence, inhibition of RIAM can inhibit spontaneous Tconv cell–mediated autoimmune colitis while preserving T reg cell trafficking and function.
Distinct integrin activation pathways for effector and regulatory T cell trafficking and function
Disclosures: M.H. Ginsberg reported personal fees from the Allen Institute of Immunology, grants from Eli Lilly Co., and grants from TrexBio outside of the submitted work. No other disclosures were reported.
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Hao Sun, Frederic Lagarrigue, Hsin Wang, Zhichao Fan, Miguel Alejandro Lopez-Ramirez, John T. Chang, Mark H. Ginsberg; Distinct integrin activation pathways for effector and regulatory T cell trafficking and function. J Exp Med 1 February 2021; 218 (2): e20201524. doi: https://doi.org/10.1084/jem.20201524
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