TLR2 deletion promotes arthritis through reduction of IL-10

Qi Quan Huang, Renee E. Koessler, Robert Birkett, Harris Perlman, Lianping Xing, Richard M. Pope

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)751-759
Number of pages9
JournalJournal of Leukocyte Biology
Volume93
Issue number5
DOIs
StatePublished - Apr 2013

Keywords

  • Cytokine
  • IgG Fc receptor
  • Inflammation
  • Macrophage
  • Oste oclastogenesis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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