IL-10 and IL-27 producing dendritic cells capable of enhancing IL-10 production of T cells are induced in oral tolerance

Shiokawa, Aya; Tanabe, Koichiro; Tsuji, Noriko M.; Sato, Ryuichiro; Hachimura, Satoshi

doi:10.1016/j.imlet.2009.05.002

Cited by 40 publications

(37 citation statements)

References 50 publications

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“…Both MDSC and tolerogenic DCs produce IL-10, the other immunosuppressive cytokine found to be negatively correlated with OS in this study (41–43). Previous studies reported significantly elevated IL-10 levels in the peripheral blood of PDAC patients (21, 44), however this is the first study to report a significant negative correlation association between circulating IL-10 levels and OS in PDAC.…”

Section: Discussionsupporting

confidence: 49%

Systemic Immune Activity Predicts Overall Survival in Treatment-Naïve Patients with Metastatic Pancreatic Cancer

Farren

Mace

Geyer

et al. 2016

Clinical Cancer Research

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Purpose: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a 5-year survival rate <7% and is ultimately refractory to most treatments. To date, an assessment of immunologic factors relevant to disease has not been comprehensively performed for treatment-na€ ve patients. We hypothesized that systemic immunologic biomarkers could predict overall survival (OS) in treatment-na€ ve PDAC patients.Experimental Design: Peripheral blood was collected from 73 patients presenting with previously untreated metastatic PDAC. Extensive immunologic profiling was conducted to assess relationships between OS and the level of soluble plasma biomarkers or detailed immune cell phenotypes as measured by flow cytometry.Results: Higher baseline levels of the immunosuppressive cytokines IL6 and IL10 were strongly associated with poorer OS (P ¼ 0.008 and 0.026, respectively; HR ¼ 1.16 and 1.28, respectively), whereas higher levels of the monocyte chemoattractant MCP-1 were associated with significantly longer OS Conclusions: These data support the hypothesis that baseline immune status predicts PDAC disease course and overall patient survival. To our knowledge, this work represents the largest cohort and most comprehensive immune profiling of treatment-na€ ve metastatic PDAC patients to date.

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Section: Discussionsupporting

confidence: 49%

Systemic Immune Activity Predicts Overall Survival in Treatment-Naïve Patients with Metastatic Pancreatic Cancer

Farren

Mace

Geyer

et al. 2016

Clinical Cancer Research

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“…Studies demonstrated that c-Maf regulated the expression of IL-10 under Th1 and Th17 cell polarization condition4649 and the enforced c-Maf expression induced IL-10 and IL-4 production in T cells. Several reports showed that IL-27 cooperated with TGF-β in activation of c-Maf and lead to the induction of IL-10-producing CD4 + Foxp3 − Tr1 cells19202127505152. Adoptive transfer of B cells attenuated DSS-induced colitis in an IL-10-independent manner11 and B cells ameliorated T-cell-mediated inflammatory bowel disease by inducing Tr1 cells in an IL-27-depedent manner10.…”

Section: Discussionmentioning

confidence: 99%

Characterization of c-Maf+Foxp3− Regulatory T Cells Induced by Repeated Stimulation of Antigen-Presenting B Cells

Chien

Chen

et al. 2017

Sci Rep

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The role of B cells in the development of CD4+ regulatory T cells has been emphasized recently. Our previous studies have demonstrated that the antigen-presenting splenic B cells converted naïve CD4+CD25− T cells into CD4+CD25+Foxp3− T cells without additional cytokines or chemicals with regulatory activity and that referred to as Treg-of-B cells. The present study further showed that Treg-of-B cells increased the IL-10-producing population, and the expression of c-Maf, inducible T-cell co-stimulator (ICOS) as well as cytotoxic T-lymphocyte-associated protein 4 (CTLA4) after repeated stimulation of B cells in a cell-cell contact-dependent manner. Long-term cultured Treg-of-B cells exerted IL-10 and CTLA4-mediated antigen-specific suppressive activity; moreover, the single antigen-specific Treg-of-B cells inhibited in a non-antigen-specific fashion. In conclusion, these results suggest that repeated stimulation of B cells induced IL-10-producing CD4+Foxp3− regulatory T cells in a contact-dependent manner and these Treg-of-B cells possess IL-10 and CTLA4-dependent suppressive function.

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“…IL-27 promotes oral tolerance 50 and mediates the ability of Bifidobacterium infantis to suppress IL-17 expression. 51 Additionally, IL-27 was elevated in Fat-1 mice in chronic DSS-induced colitis in association with improved histopathology scores and decreased expression of Th17 cell cytokines.…”

Section: Il-27 As a Therapy For Ibd: Evidence From Human Patients Andmentioning

confidence: 99%

Interleukin-27 as a Novel Therapy for Inflammatory Bowel Disease

Andrews

McLean

Durum

2016

Inflammatory Bowel Diseases

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Inflammatory bowel disease (IBD) is an inflammatory disorder of the intestine that affects an estimated 329 per 100,000 people in the United States and is increasing in incidence within a number of cultures worldwide. Likely due to its incompletely understood pathophysiology and etiology, standard treatments for IBD are only efficacious in subsets of patients and often do not induce lasting remission. As a result, novel therapies are needed. The success of anti-tumor necrosis factor-α treatment in a subset of IBD patients demonstrated that therapy targeting a single cytokine could be efficacious in IBD, and clinical trials investigating the blockade of a variety of cytokines have commenced. IL-27 is a relatively recently discovered type I cytokine with established roles in infectious disease, autoimmunity, and cancer in a variety of organs. IL-27 was identified as a candidate gene for IBD, and a number of studies in mouse models of IBD have demonstrated that IL-27 therapy is protective. However, in contrast to these investigations, genetic deletion of the IL-27 receptor has been shown to be protective in some mouse models of IBD. The purpose of this review is to highlight recent literature investigating the role of IL-27 in IBD, and to discuss possible explanations for the sometimes conflicting results of these studies. Evidence supporting IL-27 therapy as a treatment for IBD will also be discussed.

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IL-10 and IL-27 producing dendritic cells capable of enhancing IL-10 production of T cells are induced in oral tolerance

Cited by 40 publications

References 50 publications

Systemic Immune Activity Predicts Overall Survival in Treatment-Naïve Patients with Metastatic Pancreatic Cancer

Systemic Immune Activity Predicts Overall Survival in Treatment-Naïve Patients with Metastatic Pancreatic Cancer

Characterization of c-Maf+Foxp3− Regulatory T Cells Induced by Repeated Stimulation of Antigen-Presenting B Cells

Interleukin-27 as a Novel Therapy for Inflammatory Bowel Disease

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