Pattern recognition receptors and their involvement in the pathogenesis of arthritis.
OBJECTIVE
Pattern recognition receptors are germ-line encoded receptors that recognize specific pathogen-associated molecules, thereby allowing the innate immune system to distinguish self from nonself structures. Pattern recognition receptors mediate activation of different signaling pathways, resulting in the production of proinflammatory cytokines and the expression of antimicrobial genes. Additionally, pattern recognition receptors play a central role in the activation and direction of the adaptive immune response. This review summarizes recent advances in research trying to elucidate the link between different pattern recognition receptors and inflammatory autoimmune disorders.


RESULTS
The best known pattern recognition receptors, the toll-like receptors, are involved in the regulation of inflammation during infectious diseases. They affect apoptotic pathways and dendritic cell maturation, and interact with B-cell receptors in priming T-cell responses to host-derived DNA. This brought toll-like receptors and other pattern recognition receptors into focus as potential players in the induction of autoimmune diseases. Indeed, several inflammatory autoimmune diseases have been linked during the past few years to defects or polymorphisms of genes encoding pattern recognition receptors.


CONCLUSIONS
The discovery of toll-like receptors and other groups of pattern recognition receptors, such as the caspase recruitment domains or the triggering receptors expressed by myeloid cells, allowed one to draw an increasingly complex picture of immune responses to pathogens. The growing evidence for an involvement of pattern recognition receptors in the pathogenesis of autoimmune disorders warrants further investigation of the expression and function of pattern recognition receptors to develop novel therapeutics for diseases such as rheumatoid arthritis.
Seibl
Reinhart
R
Zurich University Children's Hospital, Division for Immunology, Zurich, Switzerland.
Kyburz
Diego
D
Lauener
Roger P
RP
Gay
Steffen
S
D048868:Adaptor Proteins, Signal Transducing; D001168:Arthritis / Q000276:immunology*; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins / Q000276:immunology; D006162:Guanylate Cyclase / Q000276:immunology; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology; D053474:Nod1 Signaling Adaptor Protein; D011956:Receptors, Cell Surface / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology; D051193:Toll-Like Receptors; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
D048868:Adaptor Proteins, Signal Transducing; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; C110546:TYROBP protein, human; D051193:Toll-Like Receptors; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; C426243:CARD14 protein, human; D006162:Guanylate Cyclase