Search

Abstract Background Therapeutic potential of helminth have been shown to have a protective effect on immune-mediated diseases such as Crohn's disease (CD), which is associated with increased production of T helper cell type 1. However, helminth therapy is unacceptable to patients due to side-effects and the fear of parasites. As helminths regulate the cellular immune responses through innate cells such as dendritic cells (DCs), cellular immunotherapy has been considered a therapeutic option to treat CD. Methods Bone marrow-dendritic cells were generated, enriched and treated with Trichinella spiralis muscle larval excretory/secretory products (Ts -MLES). DCs maturation was measured by flow cytometry and cytokine production of DCs were measured by ELISA. Colitis was generated by intrarectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) solution. For adoptive transfer, Ts -MLES treated-DCs injected intravenously 24 h prior to TNBS challenge. Disease activity index (DAI) including weight loss, diarrhea, and bloody stool were measured. Colon segments were stained with hematoxylin and eosin (H.E.) and periodic acid schiff (PAS) staining for histological damage scoring. The relative mRNA expression of cytokines in colon was analyzed by RT-PCR. Cytokine production in colon was measured by ELISA. Splenocytes were separated and cytokine profiles including Th1 (IFN-γ), Th2 (IL-4, IL-13), and Treg subsets (IL-10, TGF-β) were analyzed by flow cytometry. Results Ts -MLES regulated the maturation and cytokine production of DCs. Ts -MLES -DC ameliorated the severity of the TNBS-induced colitis. In the colon and the spleen, Ts -MLES-DC decreased IFN-γ (Th1) significantly and increased Th2 (IL-4, IL-13)- and Treg (IL-10, TGF-β)- related cytokines. Conclusions Ts -MLES-DC ameliorated the severity of the TNBS-induced colitis through decreasing IFN-γ. Ts -MLES-DC skewed the Th1-mediated response toward the Th2 type and regulatory T cell response. Highlights • T. spiralis MLES (Ts -MLES) regulated DCs phenotype. • Ts -MLES-DC ameliorated the severity of the TNBS-induced colitis • Ts -MLES-DC inhibited Th1 immune response while enhancing the Th2 and Treg immune response in TNBS-induced colitis in vivo. [ABSTRACT FROM AUTHOR]

• rTs-ADSp-7 alleviated the severity of TNBS-induced colitis. • rTs-ADSp-7 increased the population of Th2 and Treg cells in TNBS-induced colitis mice. • rTs-ADSp-7 protein has the potential to treat colitis or other Th1 immune-mediated diseases. Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is a chronic autoimmune disease. At present, worms and their products has been shown to have protective effects on immune-mediated diseases. Therefore, we aimed to investigate the effect of the recombination Trichinella spiralis (T. spiralis, Ts) adult serine protease-like protein r Ts -ADSp-7 on a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD mouse model. Colitis was induced by intrarectal administration of a TNBS solution. The disease activity index (DAI), which included weight loss, diarrhoea, and bloody stool, was measured. Colon segments were stained with haematoxylin and eosin (H.E.) for histopathological score. Cytokine release in the serum was analysed by meso scale discovery (MSD). Cytokine release in the colon was detected by ELISA. Splenocytes were separated, and the cytokine profiles of Th1 (IFN-γ), Th2 (IL-4), Th17 (IL-17A) and Treg cells were analysed by flow cytometry. Our result showed that rTs-ADSp-7 reduced the clinical disease activity of TNBS-induced colitis in mice. In addition, we found that r Ts -ADSp-7 reduced the production of Th1- and Th17-related cytokines while upregulating the expression of Th2- and Treg-related cytokines in TNBS-induced colitis mice. r Ts -ADSp-7 also increased the population of Th2 and Treg cells in TNBS-induced colitis mice. r Ts -ADSp-7 alleviated the severity of TNBS-induced colitis while balancing the CD4+ T cell immune response. r Ts -ADSp-7 has therapeutic potential for colitis treatment and can be used as a helminth-derived protein therapy for CD or other Th1 immunity-mediated diseases. [ABSTRACT FROM AUTHOR]