Bone marrow mesenchymal stem cells (BMSC) have been shown to possess immunomodulatory activities, while its role in rheumatoid arthritis (RA) remains unknown. Citrullinated fibrinogen (cfb) has been considered as a specific autoantigen in RA pathogenesis. Our study aims to determine the role of cfb on immunomodulatory function of BMSC. We demonstrated the specific role of toll-like receptor 4 (TLR4)-NFκB pathway in the pro-inflammatory response of BMSC to cfb with increased production of interleukin (IL)-6, IL-8 and chemokine CC motif ligand 2 (CCL2). Moreover, cfb impaired BMSC-mediated suppression of peripheral blood mononuclear cells (PBMC) proliferation and reduced the production of the key immunomodulatory molecule indoleamine 2,3-dioxygenase (IDO) in BMSC. We have uncovered a previously unrecognized role of cfb in interfering BMSC-mediated immunoregulation in RA. Cfb could act as a damage-associated molecule pattern (DAMP) for BMSC and thereby contribute to the propagation of inflammation in RA.

骨髓间充质干细胞（BMSC）已显示具有免疫调节活性，而其在类风湿关节炎（RA）中的作用仍然未知。瓜氨酸纤维蛋白原（cfb）被认为是RA发病机理中的一种特异的自身抗原。我们的研究旨在确定cfb在BMSC免疫调节功能中的作用。我们证明了Toll样受体4（TLR4）-NFκB通路在BMSC对cfb的促炎反应中具有白介素（IL）-6，IL-8和趋化因子C产生增加的特定作用C基序配体2（CCL2）。此外，cfb损害了BMSC介导的外周血单核细胞（PBMC）增殖抑制，并减少了BMSC中关键免疫调节分子吲哚胺2,3-二加氧酶（IDO）的产生。我们发现了以前无法识别的cfb在干扰BMSC介导的RA中免疫调节中的作用。Cfb可以作为BMSC的损伤相关分子模式（DAMP），从而有助于RA中炎症的传播。