Journal
ACTA PHARMACOLOGICA SINICA
Volume 41, Issue 6, Pages 800-812Publisher
NATURE PUBL GROUP
DOI: 10.1038/s41401-019-0337-2
Keywords
IgD; IgDR; IgD-Fc-Ig fusion protein; CD4(+) T cell; collagen-induced-arthritis; IgD-IgDR-Lck-NF-kappa B signaling; etanercept
Funding
- National Natural Science Foundation of China [U1803129, 81973332, 81673444]
Ask authors/readers for more resources
IgD-Fc-Ig fusion protein, a new biological agent, is constructed by linking a segment of human IgD-Fc with a segment of human IgG1-Fc, which specifically blocks the IgD-IgDR pathway and selectively inhibits the abnormal proliferation, activation, and differentiation of T cells. In this study we investigated whether IgD-Fc-Ig exerted therapeutic effects in collagen-induced arthritis (CIA) rats. CIA rats were treated with IgD-Fc-Ig (1, 3, and 9 mg/kg) or injected with biological agents etanercept (3 mg/kg) once every 3 days for 40 days. In the PBMCs and spleen lymphocytes of CIA rats, both T and B cells exhibited abnormal proliferation; the percentages of CD3(+) total T cells, CD3(+)CD4(+) Th cells, CD3(+)CD4(+)CD25(+)-activated Th cells, Th1(CD4(+)IFN-gamma(+)), and Th17(CD4(+)IL-17(+)) were significantly increased, whereas the Treg (CD4(+)CD25(+)Foxp3(+)) cell percentage was decreased. IgD-Fc-Ig administration dose-dependently decreased the indicators of arthritis; alleviated the histopathology of spleen and joint; reduced serum inflammatory cytokines levels; decreased the percentages of CD3(+) total T cells, CD3(+)CD4(+) Th cells, CD3(+)CD4(+)CD25(+)-activated Th cells, Th1 (CD4(+)IFN-gamma(+)), and Th17(CD4(+)IL-17(+)); increased Treg (CD4(+)CD25(+)Foxp3(+)) cell percentage; and down-regulated the expression of key molecules in IgD-IgDR-Lck-NF-kappa B signaling (p-Lck, p-ZAP70, p-P38, p-NF-kappa B65). Treatment of normal T cells with IgD (9 mu g/mL) in vitro promoted their proliferation. Co-treatment with IgD-Fc-Ig (0.1-10 mu g/mL) dose-dependently decreased IgD-stimulated T cell subsets percentages and down-regulated the IgD-IgDR-Lck-NF-kappa B signaling. In summary, this study demonstrates that IgD-Fc-Ig alleviates CIA and regulates the functions of T cells through inhibiting IgD-IgDR-Lck-NF-kappa B signaling.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available