JAK1-STAT3 blockade by JAK inhibitor SHR0302 attenuates inflammatory responses of adjuvant-induced arthritis rats and decreases Th17 and total B cells

Abstract

Objective: To investigate the effects of JAK inhibitor (SHR0302) on adjuvant-induced arthritis (AA) rats and the partial mechanisms focused on T, B lymphocyte subsets through JAK1-STAT3 pathway, including Th17, Treg, total B cells and memory B cells.

Methods: Animals were divided randomly into normal control, AA, SHR0302 (0.3,1.0, 3.0mg/kg) and MTX. The effects of SHR0302 on AA rats by evaluating arthritis index, arthritis global assessment and paw swelling degree, histopathology of joint and spleen. We examined the proliferation of T, B and FLS. Th17, Treg, total B and memory B cell proportion was measured by flow cytometry. Cytokines TNF-α, IL-1β, IL-10, IL-17 and antibody IgG1, IgG2a levels in serum were measured by Elisa. The expression of p-JAK1 and p-STAT3 was measured by western blot.

Results: SHR0302 suppressed the severity of AA rats by attenuating the arthritis index, arthritis global assessment and paw swelling degree, and alleviated histopathology of spleen and joint of AA rats. SHR0302 can inhibit the proliferation of T, B and FLS, and down-regulated cytokines TNF-α, IL-1β, IL-17 and antibody IgG1, IgG2a levels, and suppressed the proportion of Th17 and total B, and inhibited JAK1-STAT3 phosphorylation. There was no significant effect on Treg function and memory B cell proportion.

Conclusion: SHR0302 may attenuate the severity of AA rats, partially through reducing Th17 function and total B cell proportion by inhibiting JAK1-STAT3 phosphorylation.

Keywords: Adjuvant-induced arthritis; JAK inhibitor; Memory B cells; STAT3; Th17; Treg.