title: TLR2 deletion promotes arthritis through reduction of IL-10.
abstract: RA is a chronic inflammatory disease characterized by the persistent expression of inflammatory cytokines from macrophages, which may be mediated, in part, through TLR2 signaling. Earlier studies demonstrate a role for TLR2 signaling in dampening the arthritis in IL-1Ra-/- mice, which was mediated through T cells. This study was performed to determine whether TLR2 signaling plays a role in the pathogenesis of T cell-independent arthritis triggered by transferring serum from K/BxN mice. We documented more severe arthritis in Tlr2-/- mice compared with WT controls. The Tlr2-/- mice also demonstrated increased inflammation, erosion, pannus formation, and osteoclastogenesis, as well as increased IL-1β and decreased IL-10 within the joints. In vitro bone marrow-differentiated macrophages expressed comparable levels of activating and inhibitory FcγRs, however when stimulated with immune complexes, the Tlr2-/- macrophages expressed decreased IL-10 and reduced activation of Akt and ERK. Our findings indicate that Tlr2-/- promotes the effector phase of arthritis through decreased IL-10 by macrophages, which is important, not only as an anti-inflammatory cytokine but also in restraining the differentiation and activation of osteoclasts.
authors: Department of Medicine/Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611-2909, USA.
authors: Qi-Quan
authors: QQ
authors: Huang
authors: Renee E
authors: RE
authors: Koessler
authors: Robert
authors: R
authors: Birkett
authors: Harris
authors: H
authors: Perlman
authors: Lianping
authors: L
authors: Xing
authors: Richard M
authors: RM
authors: Pope
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology* / Q000276:immunology; D016753:Interleukin-10 / Q000502:physiology*; D053583:Interleukin-1beta / Q000502:physiology; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000502:physiology; D011961:Receptors, Fc / Q000032:analysis; D051195:Toll-Like Receptor 2 / Q000502:physiology*
chemical_list: D053583:Interleukin-1beta; D011961:Receptors, Fc; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D016753:Interleukin-10