FoxP3+ T regulatory cells and immunomodulation after Schistosoma mansoni egg antigen immunization in experimental model of inflammatory bowel disease

Hasby, Eiman Adel; Saad, Marwa A. Hasby; Shohieb, Zeinab; Noby, Kholoud El

doi:10.1016/j.cellimm.2015.02.013

Cited by 32 publications

(30 citation statements)

References 45 publications

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“…Similar outcomes of CD4 + CD25 − Foxp3 + T cells and their functions were reported in animal models of experimental colitis [ 63 ]. It is Foxp3 but not CD25 expression that plays an important role in Tregs functioning of the mouse model [ 61 , 64 ]. Thus we presumed that this phenomenon might be linked to use of purified protein which took responsibility for the uptrend of CD4 + CD25 − Foxp3 + population [ 65 ].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic potential of recombinant cystatin from Schistosoma japonicum in TNBS-induced experimental colitis of mice

et al. 2016

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BackgroundHelminth infections and their components have been shown to have a protective effect on autoimmune diseases. The isolated purified protein from Schisotosoma japonicum and its potential therapeutic effect on trinitrobenzene sulfonic acid (TNBS)-induced colitis could provide an alternative way to treat inflammatory bowel disease (IBDs).MethodsColitis was induced in Balb/c mice by rectal administration of 2.5 % TNBS, followed by intraperitoneal injection of rSjcystatin 50 μg at 6 h and 24 h afterwards. The inflammation was monitored by recording weight change, stool character and bleeding, colon length, macroscopic score (MAO), microscopic score (MIO), myeloperoxidase activity (MPO) and disease activity index (DAI). The potential underlying mechanism was investigated by examining cytokine profiles including Th1 (IFNγ), Th2 (IL-4), Th17 (IL-17A) and Treg subsets from lymphocytes of spleen, mesenteric lymph nodes (MLN) and intestinal lamina propria mononuclear cells (LPMCs) by flow cytometry. The mRNA relative expressions of the cytokines in splenocytes and MLN were analysed by quantitative real time reverse-transcriptase polymerase chain reaction (qRT-PCR). Simultaneously, the concentrations of the cytokines in the colon homogenate supernatants were tested by enzyme-linked immunosorbent assay (ELISA) and key transcription factors were detected by Western blotting.ResultsAdministration of rSjcystatin significantly reduced inflammatory parameters and ameliorated the severity of the TNBS-induced colitis through decreasing IFNγ in three organs and lifting the level of IL-4, IL-13, IL-10, and TGF-β in the colon tissues, with uptrending Tregs in the MLN and LPMC.ConclusionThe findings provide evidence that rSjcystatin has a therapeutic potential for diminishing colitis inflammation in Balb/c mice. The immunological mechanism may involve the down-regulation of Th1 response and up-regulation of Th2 and Tregs in the MLN and colon.

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Section: Discussionmentioning

confidence: 99%

Therapeutic potential of recombinant cystatin from Schistosoma japonicum in TNBS-induced experimental colitis of mice

et al. 2016

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“…Schistosoma japonicum ( S. japonicum ) and Schistosoma mansoni ( S. mansoni ) egg antigens have significant modulatory effect on DSS-induced colitis and can inhibit asthma development in murine models 28 , 29 , and S. japonicum ova can prevent epithelial damage and maintain epithelial barrier function in TNBS-induced colitis 30 . Helminths usually induce chronic infections that do not kill the host and have evolved a wide variety of approaches to suppress the immune response.…”

Section: Introductionmentioning

confidence: 99%

rSj16 Protects against DSS-Induced Colitis by Inhibiting the PPAR-α Signaling Pathway

Wang

Xie

et al. 2017

Theranostics

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Background: Epidemiologic studies and animal model experiments have shown that parasites have significant modulatory effects on autoimmune disorders, including inflammatory bowel disease (IBD). Recombinant Sj16 (rSj16), a 16-kDa secreted protein of Schistosoma japonicum (S.japonicum) produced by Escherichia coli (E. coli), has been shown to have immunoregulatory effects in vivo and in vitro. In this study, we aimed to determine the effects of rSj16 on dextran sulfate sodium (DSS)-induced colitis.Methods: DSS-induced colitis mice were treated with rSj16. Body weight loss, disease activity index (DAI), myeloperoxidase (MPO) activity levels, colon lengths, macroscopic scores, histopathology findings, inflammatory cytokine levels and regulatory T cell (Treg) subset levels were examined. Moreover, the differential genes expression after treated with rSj16 were sequenced, analyzed and identified.Results: rSj16 attenuated clinical activity of DSS-induced colitis mice, diminished pro-inflammatory cytokine production, up-regulated immunoregulatory cytokine production and increased Treg percentages in DSS-induced colitis mice. Moreover, DSS-induced colitis mice treated with rSj16 displayed changes in the expression levels of specific genes in the colon and show the crucial role of peroxisome proliferator activated receptor α (PPAR-α) signaling pathway. PPAR-α activation diminished the therapeutic effects of rSj16 in DSS-induced colitis mice, indicating that the PPAR-α signaling pathway plays a crucial role in DSS-induced colitis development.Conclusions: rSj16 has protective effects on DSS-induced colitis, effects mediated mainly by PPAR-α signaling pathway inhibition. The findings of this study suggest that rSj16 may be useful as a therapeutic agent and that PPAR-α may be a new therapeutic target in the treatment of IBD.

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“…Studies suggest that in these autoimmune diseases both genetic factors and also environmental factors contribute to triggering the inflammatory process [89]. Researchers have shown that S. mansoni molecules from eggs and the surface of adult worm, such as glycans, possess potent activity to induce Th2 response and anti-inflammatory cytokines such as IL-10 [90, 91]. Ruyssers and colleagues [28] observed that, after injection of adult S. mansoni surface proteins in mice that had Trinitrobenzenesulfonic (TNBS) acid induced colitis, there was no significant change in the levels of IFN- γ mRNA expression in T lymphocytes isolated from inflamed tissues.…”

Section: Inflammatory and Autoimmune Diseasesmentioning

confidence: 99%

Schistosome-Derived Molecules as Modulating Actors of the Immune System and Promising Candidates to Treat Autoimmune and Inflammatory Diseases

Janssen

Santos

Muller

et al. 2016

Journal of Immunology Research

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It is long known that some parasite infections are able to modulate specific pathways of host's metabolism and immune responses. This modulation is not only important in order to understand the host-pathogen interactions and to develop treatments against the parasites themselves but also important in the development of treatments against autoimmune and inflammatory diseases. Throughout the life cycle of schistosomes the mammalian hosts are exposed to several biomolecules that are excreted/secreted from the parasite infective stage, named cercariae, from their tegument, present in adult and larval stages, and finally from their eggs. These molecules can induce the activation and modulation of innate and adaptive responses as well as enabling the evasion of the parasite from host defense mechanisms. Immunomodulatory effects of helminth infections and egg molecules are clear, as well as their ability to downregulate proinflammatory cytokines, upregulate anti-inflammatory cytokines, and drive a Th2 type of immune response. We believe that schistosomes can be used as a model to understand the potential applications of helminths and helminth-derived molecules against autoimmune and inflammatory diseases.

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FoxP3+ T regulatory cells and immunomodulation after Schistosoma mansoni egg antigen immunization in experimental model of inflammatory bowel disease

Cited by 32 publications

References 45 publications

Therapeutic potential of recombinant cystatin from Schistosoma japonicum in TNBS-induced experimental colitis of mice

Therapeutic potential of recombinant cystatin from Schistosoma japonicum in TNBS-induced experimental colitis of mice

rSj16 Protects against DSS-Induced Colitis by Inhibiting the PPAR-α Signaling Pathway

Schistosome-Derived Molecules as Modulating Actors of the Immune System and Promising Candidates to Treat Autoimmune and Inflammatory Diseases

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