Abstract
BackgroundCD4+ T cells play an important role in the initiation of an immune response by providing help to other cells. Among the helper T subsets, interferon-γ (IFN-γ)-secreting T helper 1 (Th1) and IL-17-secreting T helper 17 (Th17) cells are indispensable for clearance of intracellular as well as extracellular pathogens. However, Th1 and Th17 cells are also associated with pathogenesis and contribute to the progression of multiple inflammatory conditions and autoimmune diseases.ResultsIn the current study, we found that BJ-1108, a 6-aminopyridin-3-ol analogue, significantly inhibited Th1 and Th17 differentiation in vitro in a concentration-dependent manner, with no effect on proliferation or apoptosis of activated T cells. Moreover, BJ-1108 inhibited differentiation of Th1 and Th17 cells in ovalbumin (OVA)-specific OT II mice. A complete Freund’s adjuvant (CFA)/OVA-induced inflammatory model revealed that BJ-1108 can reduce generation of proinflammatory Th1 and Th17 cells. Furthermore, in vivo studies showed that BJ-1108 delayed onset of disease and suppressed experimental autoimmune encephalomyelitis (EAE) disease progression by inhibiting differentiation of Th1 and Th17 cells.ConclusionsBJ-1108 treatment ameliorates inflammation and EAE by inhibiting Th1 and Th17 cells differentiation. Our findings suggest that BJ-1108 is a promising novel therapeutic agent for the treatment of inflammation and autoimmune disease.
Highlights
CD4+ T cells play an important role in the initiation of an immune response by providing help to other cells
We found that BJ-1108 significantly suppressed Th cell function by inhibiting T helper 1 (Th1) and T helper 17 (Th17) differentiation and marginally decreased proliferation of activated T cells without apoptosis
We found that BJ-1108 treatment reduced Th1 and Th17 generation in a complete Freund’s adjuvant (CFA)/OVA-immunized inflammatory model
Summary
CD4+ T cells play an important role in the initiation of an immune response by providing help to other cells. Th1 and Th17 cells are associated with pathogenesis and contribute to the progression of multiple inflammatory conditions and autoimmune diseases. Naïve CD4+ T cells undergo differentiation and expansion of distinct effector subsets, which play a major role in mediating immune responses through the secretion of specific cytokines [2, 3]. Th1 cells participate in the elimination of intracellular pathogens and regulation of organ-specific autoimmune diseases [1]. Th17 cells enhance immune responses against extracellular pathogens, bacteria and fungi, as well as tissue inflammation [2, 6]. Unrestrained activation of Th1 and Th17 cells is associated with autoimmune and inflammatory disorders such as multiple sclerosis, rheumatoid arthritis, and psoriasis [7, 8]
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