Schistosoma japonicum peptide SJMHE1 inhibits acute and chronic colitis induced by dextran sulfate sodium in mice

Wenqi Shan,Xuefeng Wang,Yu Zheng,Liyang Dong,Ting Wang,Fei Xue,Ming Chang,Yongbin Ma,Guoyue Yuan,Dingqi Feng,Wenzhe Zhang

doi:10.1186/s13071-021-04977-y

Abstract

BackgroundHarnessing helminth-based immunoregulation is a novel therapeutic strategy for many immune dysfunction disorders, including inflammatory bowel diseases (IBDs). We previously identified a small molecule peptide from Schistosoma japonicum and named it SJMHE1. SJMHE1 can suppress delayed-type hypersensitivity, collagen-induced arthritis and asthma in mice. In this study, we assessed the effects of SJMHE1 on dextran sulfate sodium (DSS)-induced acute and chronic colitis.MethodsAcute and chronic colitis were induced in C57BL/6 mice by DSS, following which the mice were injected with an emulsifier SJMHE1 or phosphate-buffered saline. The mice were then examined for body weight loss, disease activity index, colon length, histopathological changes, cytokine expression and helper T (Th) cell subset distribution.ResultsSJMHE1 treatment significantly suppressed DSS-induced acute and chronic colitis, improved disease activity and pathological damage to the colon and modulated the expression of pro-inflammatory and anti-inflammatory cytokines in splenocytes and the colon. In addition, SJMHE1 treatment reduced the percentage of Th1 and Th17 cells and increased the percentage of Th2 and regulatory T (Treg) cells in the splenocytes and mesenteric lymph nodes of mice with acute colitis. Similarly, SJMHE1 treatment upregulated the expression of interleukin-10 (IL-10) mRNA, downregulated the expression of IL-17 mRNA and modulated the Th cell balance in mice with chronic colitis.ConclusionsOur data show that SJMHE1 provided protection against acute and chronic colitis by restoring the immune balance. As a small molecule, SJMHE1 might be a novel agent for the treatment of IBDs without immunogenicity concerns.Graphical abstract

Highlights

Harnessing helminth-based immunoregulation is a novel therapeutic strategy for many immune dysfunction disorders, including inflammatory bowel diseases (IBDs)
We found that SJMHE1 treatment regulated cytokine expression in the colon and splenocytes and modulated helper T (Th) cell balance in splenocytes and mesenteric lymph nodes (MLNs) in mice with acute and chronic colitis
SJMHE1 treatment alleviates dextran sulfate sodium (DSS)‐induced acute colitis in mice Acute colitis was induced in mice provided with 2.5% DSS in the drinking water continuously for 10 days

Summary

Introduction

Harnessing helminth-based immunoregulation is a novel therapeutic strategy for many immune dysfunction disorders, including inflammatory bowel diseases (IBDs). We assessed the effects of SJMHE1 on dextran sulfate sodium (DSS)-induced acute and chronic colitis. In recent years the incidence of IBD has steadily increased worldwide, including in China [1]. Patients with these conditions are mainly treated with conventional medications, including corticosteroids (e.g. budesonide and prednisone) and immunomodulators (e.g. azathioprine and methotrexate). Almost all available drugs for the treatment of IBD have adverse side effects. Biologics, such as cytokines and antibodies, have high manufacturing costs that represent a major challenge to their use in IBD management [1, 4, 5]. Novel therapeutics for IBD that are safe and have minimal costs should be developed

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