title: Taking the STING out of TLR-driven autoimmune diseases: good, bad, or indifferent?
abstract: 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.
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.|Program in Innate Immunity, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Sudesh
authors.initials: S
authors.lastname: Pawaria
authors.affiliation: Division of Infectious Disease, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; and.|Program in Innate Immunity, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Shruti
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.|Program in Innate Immunity, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Baum
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.|Program in Innate Immunity, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Nündel
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.|Program in Innate Immunity, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Busto
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.|Program in Innate Immunity, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Gravallese
authors.affiliation: Division of Infectious Disease, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; and.|Program in Innate Immunity, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Fitzgerald
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; ann.rothstein@umassmed.edu.|Program in Innate Immunity, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Ann
authors.initials: A
authors.lastname: Marshak-Rothstein
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism* / Q000473:pathology; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism*; D009696:Nucleic Acids / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D009696:Nucleic Acids; D051193:Toll-Like Receptors
keywords: Toll-like receptor; autoantibody; cGAS; systemic lupus erythematosus