In:
Arthritis & Rheumatism, Wiley, Vol. 65, No. 10 ( 2013-10), p. 2583-2593
Abstract:
Previous studies have demonstrated a protective role of Toll‐like receptor 2 (TLR‐2) and a proinflammatory function of TLR‐4 during chronic T cell–driven arthritis. The involvement of TLRs in T cell–independent arthritic processes, however, remains unclear. This study was undertaken to determine the functional significance of TLR‐2 and TLR‐4 in T cell–independent immune complex–driven arthritis. Methods Serum‐transfer arthritis was induced in wild‐type and TLR‐deficient mice by intraperitoneal injections of arthritogenic K/BxN mouse serum. Arthritis was assessed macroscopically and by histologic analysis. The influence of TLR‐2 on macrophage cytokine profile, Fcγ receptor (FcγR) expression, and response to immune complexes was determined. Results While TLR‐4, unexpectedly, did not play any significant role, TLR‐2 deficiency accelerated the onset and markedly increased the severity of acute immune complex–driven arthritis in mice. TLR‐2 deficiency resulted in a substantial increase in joint inflammation, bone erosion, and cartilage pathology, indicating a protective function of TLR‐2 in passive FcγR‐driven disease. Ex vivo study of the macrophage inflammatory phenotype revealed increased production of tumor necrosis factor α (TNFα) and interleukin‐6 (IL‐6) despite similar levels of IL‐10, along with a significant increase in FcγR‐specific response, in TLR‐2 −/− mouse macrophages early in the disease. Although distinct FcγR messenger RNA expression was not affected, cell surface protein expression of the inhibitory FcγRIIB in TLR‐2 −/− naive primary macrophages was specifically diminished, resulting in a higher proinflammatory response. Accordingly, TLR‐2 stimulation specifically up‐regulated FcγRIIB, but not the activating FcγR, on macrophages. Conclusion TLR‐2 regulates acute immune complex–driven arthritis by controlling macrophage FcγR response. Our findings indicate that the protective role of TLR‐2 is extended beyond its previously described role in promoting Treg cells during T cell–mediated arthritis.
Type of Medium:
Online Resource
ISSN:
0004-3591
,
1529-0131
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
2014367-9
detail.hit.zdb_id:
2754614-7
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