Intriguingly, intracellular signals dictating LFA-1 activation are highly conserved between migration, T cell activation, and cytolytic activity suggesting that any alterations in the signaling may cause substantial biological consequences during the host immune responses. With this highly diverse set of roles, it is unsurprising that LFA-1 has been implicated in numerous autoimmune and inflammatory conditions including inflammatory bowel disease, psoriasis, diabetes, and arthritis ( 1, 2). LFA-1 is a key T cell integrin that plays a critical role in the regulation of these functions. Precise spatial and temporal regulation of adhesion and de-adhesion is critical for immune cell development, localization, and pathogen clearance. Here, we summarize the roles of LFA-1 and ongoing studies to better understand its functions and regulation. While the downstream signaling pathways utilized by LFA-1 are vastly conserved they allow for highly disparate responses. Adhesion to LFA-1’s ligand, intracellular adhesion receptor 1 (ICAM-1) facilitates firm endothelium adhesion, prolonged contact with antigen-presenting cells, and binding to target cells for killing. Among several leukocyte-specific integrins, lymphocyte function-associated antigen-1 (LFA-1 or α Lβ 2 CD11a/CD18) is a key T cell integrin, which plays a major role in regulating T cell activation and migration. Furthermore, integrins not only facilitate adhesion but also induce intracellular signaling and have recently been uncovered as mechanosensors providing additional complexity to the signaling pathways. With 24 integrin pairs having been discovered to date, integrins are defined not only by the composition of the heterodimeric pair but by cell-type specific expression and their ligands. Central to the recruitment of T cells, integrins are cell surface receptors that regulate adhesion, signal transduction, and migration. Dysregulation of lymphocyte activation and migration can lead to impaired adaptive immunity, recurrent infections, and an array of autoimmune diseases and chronic inflammation. Maintenance of homeostatic immune surveillance and development of effective adaptive immune responses require precise regulation of spatial and temporal lymphocyte trafficking throughout the body to ensure pathogen clearance and memory generation. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY, United States
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