TY - JOUR
T1 - Sensors of the innate immune system
T2 - Their link to rheumatic diseases
AU - Theofilopoulos, Argyrios N.
AU - Gonzalez-Quintial, Rosana
AU - Lawson, Brian R.
AU - Koh, Yi T.
AU - Stern, Michael E.
AU - Kono, Dwight H.
AU - Beutler, Bruce
AU - Baccala, Roberto
N1 - Funding Information:
The work of the authors is supported by National Institute of Health grants. Space limitations precluded citation of many original publications, and we apologize for these omissions.
PY - 2010/3
Y1 - 2010/3
N2 - Evidence strongly suggests that excessive or protracted signaling, or both, by cell-surface or intracellular innate immune receptors is central to the pathogenesis of most autoimmune and autoinflammatory rheumatic diseases. The initiation of aberrant innate and adaptive immune responses in autoimmune diseases can be triggered by microbes and, at times, by endogenous molecules-particularly nucleic acids and related immune complexes-under sterile conditions. By contrast, most autoinflammatory syndromes are generally dependent on germline or de novo gene mutations that cause or facilitate inflammasome assembly. The consequent production of proinflammatory cytokines, principally interferon-α/Β and tumor necrosis factor in autoimmune diseases, and interleukin-1Β in autoinflammatory diseases, leads to the creation of autoamplification feedback loops and chronicity of these syndromes. These findings have resulted in a critical reappraisal of pathogenetic mechanisms, and provide a basis for the development of novel diagnostic and therapeutic modalities for these diseases.
AB - Evidence strongly suggests that excessive or protracted signaling, or both, by cell-surface or intracellular innate immune receptors is central to the pathogenesis of most autoimmune and autoinflammatory rheumatic diseases. The initiation of aberrant innate and adaptive immune responses in autoimmune diseases can be triggered by microbes and, at times, by endogenous molecules-particularly nucleic acids and related immune complexes-under sterile conditions. By contrast, most autoinflammatory syndromes are generally dependent on germline or de novo gene mutations that cause or facilitate inflammasome assembly. The consequent production of proinflammatory cytokines, principally interferon-α/Β and tumor necrosis factor in autoimmune diseases, and interleukin-1Β in autoinflammatory diseases, leads to the creation of autoamplification feedback loops and chronicity of these syndromes. These findings have resulted in a critical reappraisal of pathogenetic mechanisms, and provide a basis for the development of novel diagnostic and therapeutic modalities for these diseases.
UR - http://www.scopus.com/inward/record.url?scp=77949264203&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77949264203&partnerID=8YFLogxK
U2 - 10.1038/nrrheum.2009.278
DO - 10.1038/nrrheum.2009.278
M3 - Review article
C2 - 20142813
AN - SCOPUS:77949264203
SN - 1759-4790
VL - 6
SP - 146
EP - 156
JO - Nature Reviews Rheumatology
JF - Nature Reviews Rheumatology
IS - 3
ER -