Immune-checkpoint protein VISTA critically regulates the IL-23/IL-17 inflammatory axis.

ABSTRACT: V-domain Immunoglobulin Suppressor of T cell Activation (VISTA) is an inhibitory immune-checkpoint molecule that suppresses CD4⁺ and CD8⁺ T cell activation when expressed on antigen-presenting cells. Vsir ^-/- mice developed loss of peripheral tolerance and multi-organ chronic inflammatory phenotypes. Vsir ^-/- CD4⁺ and CD8⁺ T cells were hyper-responsive towards self- and foreign antigens. Whether or not VISTA regulates innate immunity is unknown. Using a murine model of psoriasis induced by TLR7 agonist imiquimod (IMQ), we show that VISTA deficiency exacerbated psoriasiform inflammation. Enhanced TLR7 signaling in Vsir ^-/- dendritic cells (DCs) led to the hyper-activation of Erk1/2 and Jnk1/2, and augmented the pro

SUBMITTER: Li N 

PROVIDER: S-EPMC5431161 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature