CD4 T Cells in IBD: Crossing the Line?

Boden, Elisa K.; Lord, James D.

doi:10.1007/s10620-017-4655-2

Cited by 12 publications

(9 citation statements)

References 8 publications

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“…Dysregulated CD4 + T cells have also been demonstrated to play a crucial role in the pathogenesis of IBD [ 23 , 24 ]. The Th subsets were detected in the splenocytes and MLNs of the mice from the normal (control), DSS, DSS/PBS and DSS/SJMHE1 groups.…”

Section: Resultsmentioning

confidence: 99%

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

Shan

Zhang

et al. 2021

Parasites Vectors

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Background Harnessing 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. Methods Acute 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. Results SJMHE1 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. Conclusions Our 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

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Section: Resultsmentioning

confidence: 99%

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

Shan

Zhang

et al. 2021

Parasites Vectors

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“…These intermediate and weakly suppressive Tregs may contribute to the impaired ability to control inflammation in autoimmune disease. Indeed, recently emergent evidence supports that locally within the intestinal lamina propria, IBD patients present with greater amounts of effector-biased plasticity in FOXP3 + Tregs (31). Through BT-11 treatment, we show the ability to rescue a regulatory phenotype.…”

Section: Discussionmentioning

confidence: 53%

Oral Treatment with BT-11 Ameliorates Inflammatory Bowel Disease by Enhancing Regulatory T Cell Responses in the Gut

Leber¹,

Hontecillas²,

Zoccoli-Rodriguez³

et al. 2019

The Journal of Immunology

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Inflammatory bowel disease (IBD) is an expanding autoimmune disease afflicting millions that remains difficult to treat due to the accumulation of multiple immunological changes. BT-11 is an investigational new drug for IBD that is orally active, gut restricted, and targets the lanthionine synthetase C-like 2 immunometabolic pathway. CD25+ FOXP3+ CD4+ T cells are increased locally within the colon of BT-11–treated mice in Citrobacter rodentium and IL-10−/− mouse models of colitis. The maintained efficacy of BT-11 in the absence of IL-10 combined with the loss of efficacy when direct cell–cell interactions are prevented suggest that the regulatory T cell (Treg)–related elements of suppression are cell contact–mediated. When PD-1 is inhibited, both in vitro and in vivo, the efficacy of BT-11 is reduced, validating this assertion. The depletion of CD25+ cells in vivo abrogated the retention of therapeutic efficacy postdiscontinuation of treatment, indicating that Tregs are implicated in the maintenance of tolerance mediated by BT-11. Furthermore, the involvement of CD25 suggested a role of BT-11 in IL-2 signaling. Cotreatment with BT-11 and IL-2 greatly enhances the differentiation of CD25+ FOXP3+ cells from naive CD4+ T cells relative to either alone. BT-11 enhances phosphorylation of STAT5, providing a direct linkage to the regulation of FOXP3 transcription. Notably, when STAT5 is inhibited, the effects of BT-11 on the differentiation of Tregs are blocked. BT-11 effectively enhances the IL-2/STAT5 signaling axis to induce the differentiation and stability of CD25+ FOXP3+ cells in the gastrointestinal mucosa to support immunoregulation and immunological tolerance in IBD.

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“…SJMHE1 treatment modulates Th cell balance in the splenocytes and MLNs in mice with DDS-induced acute colitis Dysregulated CD4 + T cells have also been demonstrated to play a crucial role in the pathogenesis of IBD [20,21]. The Th subsets were detected in the splenocytes and MLNs of the mice from normal, DSS, DSS/PBS, and DSS/SJMHE1 groups.…”

Section: Sjmhe1 Treatment Regulates Cytokine Expression In the Splenocytes And Colon In Dss-induced Acute Colitis Of Micementioning

confidence: 98%

Schistosoma Japonicum Peptide SJMHE1 Inhibits Acute And Chronic Colitis Induced By Dextran Sulphate Sodium In Mice

Shan

Zhang

Xue

et al. 2021

Preprint

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Background: Harnessing helminth-based immunoregulation is a novel therapeutic strategy for many immune dysfunction disorders, including inflammatory bowel diseases. 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. Methods: C57BL/6 mice were induced acute and chronic colitis by DSS, and were injected by emulsifier SJMHE1 or PBS. Then the mice were examined body weight loss, disease activity index, colon lengths, histopathology change, cytokine expression and helper T (Th) cell subset distribution.Results: We found that SJMHE1 treatment significantly suppressed DSS-induced acute and chronic colitis, improved disease activity and colon pathological damage. SJMHE1 treatment modulated the expression of pro-inflammatory and anti-inflammatory cytokines in splenocytes and the colon. Furthermore, 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 (MLNs) from mice with acute colitis. Similarly, SJMHE1 treatment upregulated the expression of IL-10 mRNA, and downregulated the expression of IL-17 mRNA, and modulated the Th cell balance in mice with chronic colitis. Conclusions: Our data show that SJMHE1 provided protection against acute and chronic colitis by restoring immune balance. As a small molecule, SJMHE1 might be a novel agent for the treatment of IBD without immunogenicity concerns.

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CD4 T Cells in IBD: Crossing the Line?

Cited by 12 publications

References 8 publications

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

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

Oral Treatment with BT-11 Ameliorates Inflammatory Bowel Disease by Enhancing Regulatory T Cell Responses in the Gut

Schistosoma Japonicum Peptide SJMHE1 Inhibits Acute And Chronic Colitis Induced By Dextran Sulphate Sodium In Mice

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