| First Author | Sun H | Year | 2021 |
| Journal | J Exp Med | Volume | 218 |
| Issue | 2 | PubMed ID | 33104169 |
| Mgi Jnum | J:310835 | Mgi Id | MGI:6509801 |
| Doi | 10.1084/jem.20201524 | Citation | Sun H, et al. (2021) Distinct integrin activation pathways for effector and regulatory T cell trafficking and function. J Exp Med 218(2) |
| abstractText | 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 alphaLbeta2, alpha4beta1, and alpha4beta7. 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. |
