Abstract
Delayed-type hypersensitivity arthritis (DTHA) is a recently established experimental model of rheumatoid arthritis (RA) in mice with pharmacological values. Despite an indispensable role of CD4+ T cells in inducing DTHA, a potential role for CD4+ T cell subsets is lacking. Here we have quantified CD4+ subsets during DTHA development and found that levels of activated, pro-inflammatory Th1, Th17, and memory CD4+ T cells in draining lymph nodes were increased with differential dynamic patterns after DTHA induction. Moreover, according to B-cell depletion experiments, it has been suggested that this cell type is not involved in DTHA. We show that DTHA is associated with increased levels of B cells in draining lymph nodes accompanied by increased levels of circulating IgG. Finally, using the anti-rheumatoid agents, methotrexate (MTX) and the anti-inflammatory drug dexamethasone (DEX), we show that MTX and DEX differentially suppressed DTHA-induced paw swelling and inflammation. The effects of MTX and DEX coincided with differential regulation of levels of Th1, Th17, and memory T cells as well as B cells. Our results implicate Th1, Th17, and memory T cells, together with activated B cells, to be involved and required for DTHA-induced paw swelling and inflammation.
Highlights
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease elicited by complex interactions between genetic and environmental factors, leading to chronic life-long inflammation of synovial joints [1]
Our results demonstrate that T helper 1 (Th1), T helper 17 (Th17), and memory T cells interplay with B cells in promoting Delayed-type hypersensitivity arthritis (DTHA)-induced inflammation and paw swelling
We observed a significant increase in the levels of GR1+ neutrophils, F4/80+ macrophages, CD4+ T cells, CD8+ T cells, and CD19+ B cells in the paws of DTHA-affected mice compared to normal mice (Figures 1D, E)
Summary
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease elicited by complex interactions between genetic and environmental factors, leading to chronic life-long inflammation of synovial joints [1]. Over time this may lead to progressive and severe joint destruction and deformity [2]. For treating the RA, methotrexate (MTX) is the most versatile drug used for preventing joint damage and glucocorticoids (GCs) for suppressing inflammation The combination of these two compounds is most frequently used to reduce RA progression [17,18,19,20]
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