UC San Diego

Integrins have been known for its role in facilitating cell migration. Recent studies have revealed that integrin activation also plays important roles in maintaining T cell homeostasis and peripheral tolerance, but the mechanism of integrin activation in regulatory T cells, a subset of T cells that maintains peripheral tolerance, remains obscure. Here, by using various Treg-specific gene knocked out mice, we found talin and Rap1 are critical for integrin activation in regulatory T cells. The connection between Rap1 and talin is mediated by an adaptor, RIAM. Surprisingly, RIAM knockout did not affect integrin activation in Tregs. Using mutant mice, we found another adaptor, Lamellipodin, can provide some of the connection between Rap1 and talin. In addition, we found that in lymphocytes, direct binding of Rap1 to two sites in talin makes another contribution to integrin activation in Tregs. Taken together, distinct pathways are involved in Tregs and enable their ability to maintain immune homeostasis through their suppression function.