To the Editor:

Aberrant osteopontin (OPN) production has been thought to play an important role in the pathogenesis of rheumatoid arthritis (RA) (1, 2). Recently, Chen et al (3) reported that OPN can directly influence Th17 differentiation. The effect was mediated through a mechanism that was independent of the interleukin-6 (IL-6)/STAT-3 pathway and specifically involved OPN receptors CD44 and CD29 (subunit β1) but not CD51 (subunit αv), as shown by fluorescence-activated cell sorting analysis of CD4+ T cells from healthy individuals. In parallel, production of IL-17, but not of IL-6, was significantly decreased in cultures to which antibodies to CD44 or CD29 were added. The data also showed that IL-1β production was required for CD44-mediated Th17 differentiation. Additionally, expression levels of the 3 receptors did not differ between RA patients and healthy controls (3).

However, the available data seem to be controversial. A previous study by Murugaiyan et al (4) demonstrated increased expression of OPN receptors (CD44, αv, β3, and β1) on T cells, and OPN induced IL-17 production by CD4+ T cells via the β3 integrin receptor, but not others, in experimental autoimmune encephalomyelitis. In addition, the data indicated that OPN can inhibit IL-10 expression via CD44 (4). This inconsistency may be attributed in part to the different models or experimental conditions used. However, Chen et al also reported that interferon-γ (IFNγ) production was not affected by OPN in CD4+ T cells purified from peripheral blood mononuclear cells from healthy individuals (3). In contrast, Murugaiyan and colleagues showed that induction of IFNγ was inhibited by a blocking antibody to the β3 integrin subunit. This was further confirmed by using β3 integrin–deficient mice, and T cells from these mice were nonresponsive to OPN stimulation. Moreover, recombinant mouse OPN also increased IFNγ production in normal human subjects (4).

Further studies are needed to clarify the precise mechanisms by which OPN exerts effects in RA. A better understanding of this aspect of the disease pathogenesis may be of benefit in the development of novel therapeutic strategies for autoimmune diseases.

  • 1
    Fan K, Dai J, Wang H, Wei H, Cao Z, Hou S, et al. Treatment of collagen-induced arthritis with an anti-osteopontin monoclonal antibody through promotion of apoptosis of both murine and human activated T cells. Arthritis Rheum 2008; 58: 204152.
  • 2
    Zheng W, Li R, Pan H, He D, Xu R, Guo TB, et al. Role of osteopontin in induction of monocyte chemoattractant protein 1 and macrophage inflammatory protein 1β through the NF-κB and MAPK pathways in rheumatoid arthritis. Arthritis Rheum 2009; 60: 195765.
  • 3
    Chen G, Zhang X, Li R, Fang L, Niu X, Zheng Y, et al. Role of osteopontin in synovial Th17 differentiation in rheumatoid arthritis. Arthritis Rheum 2010; 62: 29008.
  • 4
    Murugaiyan G, Mittal A, Weiner HL. Increased osteopontin expression in dendritic cells amplifies IL-17 production by CD4+ T cells in experimental autoimmune encephalomyelitis and in multiple sclerosis. J Immunol 2008; 181: 74808.

Rui-Xue Leng MD*, Hai-Feng Pan MD*, Dong-Qing Ye MD, PhD*, * Anhui Medical University, Anhui, China.