Role for toll-like receptors in autoimmune disease: the example of systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a multisystem disease characterized by an autoimmune response to nuclear antigens. Although the pathophysiology of SLE remains incompletely understood, many recent studies indicate a major role for innate immunity. The toll-like receptors (TLRs), which play a key role in innate responses to infections, are also involved in acute and chronic inflammatory processes induced by endogenous ligands. Numerous in vitro studies have established that TLR7 and TLR9 are involved in immune complex recognition. Activation of these receptors leads to activation of immune cells, most notably B cells and dendritic cells, and to the inappropriate production of many cytokines known to be directly involved in the pathogenesis of SLE. These data prompted studies in several murine models of SLE to assess the impact of inactivation or overexpression of genes encoding TLRs or molecules involved in TLR signaling pathways. The results confirmed the major role for TLR7 and suggested involvement of TLR4 in the induction of an aggressive autoimmune response. However, in vivo data suggest a protective effect of TLR9, thus contradicting the in vitro results. In humans, genetic studies have identified polymorphisms associated with increased susceptibility to SLE.
CNRS UMR 5164, 146 rue Léo-Saignat, 33076 Bordeaux, France. christophe.richez@chu-bordeaux.fr
Christophe
C
Richez
Patrick
P
Blanco
Ian
I
Rifkin
Jean-François
JF
Moreau
Thierry
T
Schaeverbeke
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000503:physiopathology*; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000503:physiopathology*; D051379:Mice; D011110:Polymorphism, Genetic / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology; D051193:Toll-Like Receptors / Q000502:physiology*
D051193:Toll-Like Receptors