%0 Journal Article
%T cGAS-activated endothelial cell-T cell cross-talk initiates tertiary lymphoid structure formation.
%A Zhao R
%A Zhang J
%A Ma J
%A Qu Y
%A Yang Z
%A Yin Z
%A Li F
%A Dong Z
%A Sun Q
%A Zhu S
%A Chen ZJ
%A Gao D
%J Sci Immunol
%V 9
%N 98
%D 2024 Aug 2
%M 39093956
%F 30.63
%R 10.1126/sciimmunol.adk2612
%X 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.