Regulatory T cells and immune computation

Quintana, Francisco J.; Cohen, Irun R.

doi:10.1002/eji.200838143

Cited by 13 publications

(7 citation statements)

References 37 publications

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“…It is known that the maturation status of DCs is crucial for the initiation of primary immune responses, and recently, it was confirmed that immature DCs are prone to induce regulatory T cells, which are a key components in maintaining immune homoeostasis and regulating immune responses in helminth infections (10–13). Although regulatory T cells were first described as differentiating in newborn thymus, it is now clear that they also develop in the periphery from nonregulatory T cells in a process termed ‘conversion’ (14). Some observations suggest that induction of regulatory T cells occurs during infections with certain pathogens, including Bordetella pertussis (15), the nematode Onchocerca volvulus (16), and schistosome infection.…”

Section: Introductionmentioning

confidence: 99%

Unique roles of Schistosoma japonicum protein Sj16 to induce IFN‐γ and IL‐10 producing CD4⁺CD25⁺ regulatory T cells in vitro and in vivo

Sun

Zhou

et al. 2012

Parasite Immunology

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Various proteins are expressed during different stages of schistosome development that are essential for cercarial penetration of vertebrate skin and evasion of host immune response. CD4(+)CD25(+) regulatory T cells are important in modulating immune responses towards helminth infections. Schistosoma japonicum protein Sj16 present in the secretions of schistosomula has been shown to have anti-inflammatory effects; however, it is uncertain whether Sj16 can induce CD4(+)CD25(+) regulatory T cells to participate in the regulation of early infection. In this study, we demonstrate a relationship between recombinant Sj16 (rSj16) and the induction of CD4(+)CD25(+) Foxp3(+) regulatory T cells. An increase in CD4(+)CD25(+) T cells was observed both in splenic cells from mice injected with rSj16 and the cells pretreated with rSj16, respectively. The induced CD4(+)CD25(+) T cells suppressed CD4(+)CD25(-) T-cell proliferation; furthermore, IFN-γ and IL-10 released from rSj16-stimulated cells contribute to this suppression. Additionally, rSj16-treated bone marrow dendritic cells (BMDCs) demonstrate an immature phenotype and play a role in the conversion of CD4(+)CD25(-) T cells into suppressive CD4(+)CD25(+) regulatory T cells. Our study identified a new CD4(+)CD25(+) T-cell population that induced by rSj16 and suggests that an IFN-γ-biased microenvironment during early infection of schistosome may favour the establishment of infection.

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Section: Introductionmentioning

confidence: 99%

Unique roles of Schistosoma japonicum protein Sj16 to induce IFN‐γ and IL‐10 producing CD4⁺CD25⁺ regulatory T cells in vitro and in vivo

Sun

Zhou

et al. 2012

Parasite Immunology

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“…Furthermore, many genes involved in immune regulation possess multiple dioxin response elements [DREs] in their promoter region. (10, 11) Studies performed in AhR −/− mice have shown an enhanced inflammatory response to cigarette smoke or endotoxin, with elevated levels of tumor necrosis factor-α [TNFα] and interleukin-6 [IL-6]. (12, 13) AhR is essential in the regulation of cell cycle, lipid metabolism (14) circadian rhythm (15) and immune response.…”

Section: Introductionmentioning

confidence: 99%

Role of the xenobiotic receptor in inflammatory bowel disease

Arsenescu

Zhong

et al. 2011

Inflammatory Bowel Diseases

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Background Gene-environment interplay modulates Inflammatory Bowel Diseases [IBD]. Dioxin-like compounds can activate the Aryl Hydrocarbon Receptor [AhR] and alter macrophage function as well as T cell polarization. We hypothesized that attenuation of the AhR signaling pathway will ameliorate colitis in a murine model of IBD. Design DSS colitis was induced in C57BL/6 AhR null mice [AhR −/−], heterozygous mice [AhR−/+], and their wild type [WT] littermates. Clinical and morphopathological parameters were used to compare the groups. Patients: AhR pathway activation was analyzed in biopsy specimens from 25 IBD patients and 15 healthy controls. Results AhR −/− mice died before the end of the treatment. However, AhR −/+ mice exhibited decreased disease activity compared to WT mice. The AhR −/+ mice expressed less proinflammatory cytokines such as TNFα (6.1 versus 15.7 fold increase) and IL17 (23.7 versus 67.9 fold increase) and increased antiinflammatory IL-10 (2.3 fold increase) compared with the AhR+/+ mice in the colon. Colonic macrophage infiltration was attenuated in the AhR −/+ group. AhR and its downstream targets were significantly upregulated in IBD patients versus control (CYP1A1 – 19.9, and IL8-10 fold increase). Conclusion Attenuation of the AhR receptor expression resulted in a protective effect during DSS-induced colitis, while the absence of AhR exacerbated the disease. Abnormal AhR pathway activation in the intestinal mucosa of IBD patients may promote chronic inflammation. Modulation of AhR signaling pathway via the diet, cessation of smoking or administration of AhR antagonists could be viable strategies for the treatment of IBD.

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“…3 Two major populations of Tregs, with complementary and overlapping functions in the control of immune response in vivo, exist, as follows: natural (or constitutive) and inducible (or adaptive) Tregs. Numerous studies have demonstrated the therapeutic use of Ag-specific Tregs in various experimental models of autoimmune diseases and allogeneic transplantation, providing long-term tolerance by active and specific regulation of self-Ag and alloantigenspecific T cells (3)(4)(5). These findings have opened up exciting opportunities for new therapies in several human diseases that are associated with Treg dysfunction.…”

mentioning

confidence: 99%

Induction of Alloantigen-Specific Human T Regulatory Cells by Vasoactive Intestinal Peptide

Pozo

Anderson

González‐Rey

2009

The Journal of Immunology

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T regulatory cells (Tregs) are instrumental in the maintenance of immunological tolerance. Although Treg-based immunotherapy proved successful in preclinical autoimmunity and transplantation, factors involved in the generation of human Ag-specific Tregs are poorly known. In this study, we show that treatment of human CD4+CD25− T cells with the cytokine-like vasoactive intestinal peptide (VIP) during in vitro stimulation induces an anergic FoxP3+CD4+CD25high T cell subset displaying potent regulatory activities against allospecific effector T cells, irrespective of the presence of naturally occurring Tregs. VIP-tolerant T cells are characterized by incapability to progress to S phase of cell cycle during stimulation with HLA-disparate APCs by negatively affecting the synthesis of cyclins D3 and E, the activation of cyclin-dependent kinases (cdk)2 and cdk4, and the down-regulation of the cdk inhibitor p27kip1. VIP interaction with the type 1 VIP receptor and subsequent activation of cAMP/protein kinase A pathway play a major role in all these effects. Moreover, VIP-tolerant T cells protect against acute graft-vs-host disease in a mouse model of allogeneic bone marrow transplantation. The infusion of VIP-tolerant T cells together with the graft significantly reduces the clinical signs and mortality rate typical of the graft-vs-host disease. These effects are mediated by impairing allogeneic haplotype-specific responses of donor CD4+ cells in the transplanted animals. Our results suggest that including alloantigen-specific VIP-generated Tregs may be a valuable tool in therapeutic interventions to promote immunotolerance toward allogeneic grafts and to reduce the need of general immunosuppressive drugs.

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Regulatory T cells and immune computation

Cited by 13 publications

References 37 publications

Unique roles of Schistosoma japonicum protein Sj16 to induce IFN‐γ and IL‐10 producing CD4⁺CD25⁺ regulatory T cells in vitro and in vivo

Unique roles of Schistosoma japonicum protein Sj16 to induce IFN‐γ and IL‐10 producing CD4⁺CD25⁺ regulatory T cells in vitro and in vivo

Role of the xenobiotic receptor in inflammatory bowel disease

Induction of Alloantigen-Specific Human T Regulatory Cells by Vasoactive Intestinal Peptide

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Regulatory T cells and immune computation

Cited by 13 publications

References 37 publications

Unique roles of Schistosoma japonicum protein Sj16 to induce IFN‐γ and IL‐10 producing CD4+CD25+ regulatory T cells in vitro and in vivo

Unique roles of Schistosoma japonicum protein Sj16 to induce IFN‐γ and IL‐10 producing CD4+CD25+ regulatory T cells in vitro and in vivo

Role of the xenobiotic receptor in inflammatory bowel disease

Induction of Alloantigen-Specific Human T Regulatory Cells by Vasoactive Intestinal Peptide

Contact Info

Product

Resources

About

Unique roles of Schistosoma japonicum protein Sj16 to induce IFN‐γ and IL‐10 producing CD4⁺CD25⁺ regulatory T cells in vitro and in vivo

Unique roles of Schistosoma japonicum protein Sj16 to induce IFN‐γ and IL‐10 producing CD4⁺CD25⁺ regulatory T cells in vitro and in vivo