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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,6,21]]},"abstract":"<jats:p>Pediatric patients with constitutively active mutations in the cytosolic double-stranded-DNA-sensing adaptor STING develop an autoinflammatory syndrome known as STING-associated vasculopathy with onset in infancy (SAVI). SAVI patients have elevated interferon-stimulated gene expression and suffer from interstitial lung disease (ILD) with lymphocyte predominate bronchus-associated lymphoid tissue (BALT). Mice harboring SAVI mutations (STING V154M [VM]) that recapitulate human disease also develop lymphocyte-rich BALT. Ablation of either T or B lymphocytes prolongs the survival of SAVI mice, but lung immune aggregates persist, indicating that T cells and B cells can independently be recruited as BALT. VM T cells produced IFN\u03b3, and IFN\u03b3R deficiency prolonged the survival of SAVI mice; however, T-cell-dependent recruitment of infiltrating myeloid cells to the lung was IFN\u03b3 independent. Lethally irradiated VM recipients fully reconstituted with wild type bone-marrow-derived cells still developed ILD, pointing to a critical role for VM-expressing radioresistant parenchymal and\/or stromal cells in the recruitment and activation of pathogenic lymphocytes. We identified lung endothelial cells as radioresistant cells that express STING. Transcriptional analysis of VM endothelial cells revealed up-regulation of chemokines, proinflammatory cytokines, and genes associated with antigen presentation. 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