{Reference Type}: Journal Article
{Title}: cGAS-activated endothelial cell-T cell cross-talk initiates tertiary lymphoid structure formation.
{Author}: Zhao R;Zhang J;Ma J;Qu Y;Yang Z;Yin Z;Li F;Dong Z;Sun Q;Zhu S;Chen ZJ;Gao D;
{Journal}: Sci Immunol
{Volume}: 9
{Issue}: 98
{Year}: 2024 Aug 2
{Factor}: 30.63
{DOI}: 10.1126/sciimmunol.adk2612
{Abstract}: Aberrant activation of the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway causes autoimmunity in humans and mice; however, the exact mechanism by which the cGAS-STING pathway initiates adaptive immunity and tissue pathology is still not fully understood. Here, we used a cGAS knockin (KI) mouse model that develops systemic autoimmunity. In the lungs of cGAS-KI mice, blood vessels were enclosed by organized lymphoid tissues that resemble tertiary lymphoid structures (TLSs). Cell-intrinsic cGAS induction promoted up-regulation of CCR5 in CD8+ T cells and led to CCL5 production in vascular endothelial cells. Peripheral CD8+ T cells were recruited to the lungs and produced CXCL13 and interferon-γ. The latter triggered endothelial cell death, potentiated CCL5 production, and was essential for TLS establishment. Blocking CCL5 or CCR5, or depleting CD8+ T cells, impaired TLS formation. cGAS-mediated TLS formation also enhanced humoral and antitumor responses. These data demonstrate that cGAS signaling drives a specialized lymphoid structure that underlies autoimmune tissue pathology.