Taking the STING out of TLR-driven autoimmune diseases: good, bad, or indifferent
Department of Medicine, Division of Rheumatology; Department of Medicine, Division of Infectious Diseases and Immunology; Program in Innate Immunity
Cell Biology | Immune System Diseases | Immunology and Infectious Disease
Both endosomal and cytosolic-nucleic acid-sensing receptors can detect endogenous ligands and promote autoimmunity and autoinflammation. These responses involve a complex interplay among and between the cytosolic and endosomal sensors involving both hematopoietic and radioresistant cells. Cytosolic sensors directly promote inflammatory responses through the production of type I IFNs and proinflammatory cytokines. Inflammation-associated tissue damage can further promote autoimmune responses indirectly, as receptor-mediated internalization of the resulting cell debris can activate endosomal Toll-like receptors (TLR). Both endosomal and cytosolic receptors can also negatively regulate inflammatory responses. A better understanding of the factors and pathways that promote and constrain autoimmune diseases will have important implications for the development of agonists and antagonists that modulate these pathways.
Toll-like receptor, autoantibody, cGAS, systemic lupus erythematosus
DOI of Published Version
J Leukoc Biol. 2017 Jan;101(1):121-126. doi: 10.1189/jlb.3MR0316-115R. Epub 2016 Aug 16. Link to article on publisher's site
Journal of leukocyte biology
Pawaria, Sudesh; Sharma, Shrutie; Baum, Rebecca; Nundel, Kerstin; Busto, Patricia; Gravallese, Ellen M.; Fitzgerald, Katherine A.; and Marshak-Rothstein, Ann, "Taking the STING out of TLR-driven autoimmune diseases: good, bad, or indifferent" (2017). University of Massachusetts Medical School Faculty Publications. 1218.