Tofacitinib promotes myeloid-derived suppressor cells expansion and reduces disease severity of arthritis SKG mice

 

Myeloid-derived suppressor cells (MDSCs) are mix cell population that interfere rheumatoid arthritis (RA) immune response by inhibiting T cell responses. Previous studies have shown tofacitinib, a JAK inhibitor, is a novel therapeutic strategy against RA. Nishimura et al. revealed the effects of tofacitinib on MDSCs in SKG mice with induced RA. The article was published on Arthritis Rheumatol.

 

In RA patients, cytokine production by dendritic cells, monocytes, T cells, B cells and neutrophils in the joint contributes to the pathogenesis. MDSCs have been reported to suppress T cell responses. This cell population is divided into two subsets: polymorphonuclear MDSCs (PMN-MDSCs) which express high ROS and low NO, and monocytic MDSCs (M-MDSCs) which express low ROS and high NO, both subsets express ArgI. In this study, researchers used zymosan A (ZyA) to induce arthritis to SKG mice, followed by transferring bone marrow (BM) MDSCs from donor arthritic SKG mice to recipient arthritic mice. The recipient arthritic mice had less disease severity compared to controls. On the other hand, tofacitinib treatment induced more MDSCs and PMN-MDSCs in the bone marrow and reduced arthritis severity in SKG mice, indicating that tofacitinib has effect on promoting MDSCs expansion and ameliorating arthritis in SKG mice.

 

Reference:
Arthritis Rheumatol. 2014 Dec 29.10.1002/art.39007.

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