Background/Purpose:  Previously, we have identified leucine-rich alpha 2 glycoprotein (LRG) as a disease marker of Rheumatoid arthritis(RA). Although LRG is produced in site of inflammation such as synovial tissues, its function is still unclear. Recently, LRG has been reported to modulate TGF-β signaling. TGF-β is essential for differentiation of Th17 and Treg, and these cells play important roles in the pathogenesis of RA, for example, by regulating osteoclast differentiation. So, LRG is may be involved in the pathogenesis of RA through the regulation of T lymphocyte differentiation. In this study, we aimed to elucidate the function of LRG on T lymphocyte differentiation and to examine the involvement of LRG in the pathogenesis of RA.

Methods: Naïve T lymphocyte were isolated from WT mice to examine the effects of LRG on the differentiation into Th17 and Treg. Male C57BL/6 mice and LRG KO mice were subjected to collagen-induced arthritis (CIA).

Results: In the presence of TGF-β alone, the differentiation of Treg was promoted by LRG. However, in the presence both TGF-β and IL6, LRG enhanced the differentiation into Th17 by increasing STAT3 phosphorylation. In CIA model, the numbers of Th17 in regional lymph nodes and serum levels of IL17 were significantly lower in LRG KO mice than in WT mice.

Conclusion: We propose that LRG promote differentiation of Th17 by enhancing phosphorylation of STAT3 and Smad in naïve T cells in the presence both TGF-b and IL6, and might involve in the arthritis pathology.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-effects-of-lrg-on-the-differentiation-of-naive-t-cells/