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Taking the STING out of TLR‐driven autoimmune diseases: good, bad, or indifferent?
Author(s) -
Pawaria Sudesh,
Sharma Shruti,
Baum Rebecca,
Nündel Kerstin,
Busto Patricia,
Gravallese Ellen M.,
Fitzgerald Katherine A.,
MarshakRothstein Ann
Publication year - 2017
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.3mr0316-115r
Subject(s) - endosome , biology , proinflammatory cytokine , microbiology and biotechnology , receptor , internalization , inflammation , autoimmunity , tlr7 , tlr9 , cytosol , immunology , innate immune system , toll like receptor , immune system , biochemistry , gene expression , dna methylation , gene , enzyme
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.