Co‐operative action of interleukin‐10 and interferon‐γ to regulate dendritic cell functions

Yanagawa, Yoshiki; Iwabuchi, Kazuya; Onoé, Kazunori

doi:10.1111/j.1365-2567.2008.02986.x

Cited by 54 publications

(35 citation statements)

References 44 publications

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“…In most recent studies, T R 1-like cells are defined by the coexpression of IL-10 and IFN-g, associated with functional competence in immunomodulation (21,22 2 CD4 + T cells of tolerant recipients may induce IDO expression in an allograft endothelial cell (38). Furthermore, IL-10 and IFN-g were found to cooperatively regulate dendritic cell functions toward immune tolerance through the augmentation of IDO (39). In our MLR model, IDO activity was enhanced by the addition of MSC-primed CD4 + R cells (Fig.…”

Section: Mscs Convert Cd4 + Cells Into Immunosuppressive T R 1-like Cmentioning

confidence: 99%

Prostaglandin E2 Potentiates Mesenchymal Stem Cell–Induced IL-10+IFN-γ+CD4+ Regulatory T Cells To Control Transplant Arteriosclerosis

Hsu

Lin

Chiang

et al. 2013

The Journal of Immunology

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Mesenchymal stem cells (MSCs) are known for their immunomodulatory functions. We previously demonstrated that bone marrow–derived MSCs effectively control transplant arteriosclerosis (TA) by enhancing IL-10+ and IFN-γ+ cells. The objective of this study is to elucidate the mechanism by which MSCs induce IL-10+IFN-γ+CD4+ regulatory T type 1 (TR1)–like cells. In an MLR system using porcine PBMCs, MSC-induced IL-10+IFN-γ+CD4+ cells, which confer resistance to allogeneic proliferation in an IL-10–dependent manner, resemble TR1-like cells. Both cyclooxygenase-derived PGE2 and IDO help to induce TR1-like cells by MSCs. MSCs constitutively secrete PGE2, which is augmented in allogeneic reactions. However, TR1-like cells were deficient in PGE2 and 4-fold less potent than were MSCs in suppressing MLR. PGE2 mimetic supplements can enhance the immunosuppressive potency of TR1-like cells. In a porcine model of allogeneic femoral arterial transplantation, MSC-induced TR1-like cells combined with PGE2, but not either alone, significantly reduced TA at the end of 6 wk (percentage of luminal area stenosis: TR1-like cells + PGE2: 11 ± 10%; PGE2 alone: 93 ± 8.7%; TR1-like cells alone: 88 ± 2.4% versus untreated 94 ± 0.9%, p < 0.001). These findings indicate that PGE2 helps MSC-induced IL-10+IFN-γ+CD4+ TR1-like cells inhibit TA. PGE2 combined with MSC-induced TR1-like cells represents a new approach for achieving immune tolerance.

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Section: Mscs Convert Cd4 + Cells Into Immunosuppressive T R 1-like Cmentioning

confidence: 99%

Prostaglandin E2 Potentiates Mesenchymal Stem Cell–Induced IL-10+IFN-γ+CD4+ Regulatory T Cells To Control Transplant Arteriosclerosis

Hsu

Lin

Chiang

et al. 2013

The Journal of Immunology

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“…PspA 199-246 -specific CD4 + T cells were able to mount both IL-10 and IFN-γ responses in either control or anti-CCL5 antibody treated mice. IL-10 and IFN-γ double-producers are found in a subpopulation of Tr1 and Th1 cells, which suppress DCs ability to activate CD4 + T cells [42]. It is tempting to speculate that the previously reported IFN-γ + IL-10 + CD4 + T cells might play some function in the T cell responsiveness attributed by CCL5.…”

Section: Discussionmentioning

confidence: 99%

CCL5-independent helper T lymphocyte responses to immuno-dominant pneumococcal surface protein A epitopes

Singh

Briles

et al. 2012

Vaccine

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Understanding the requirements for protection against pneumococcal carriage and pneumonia will greatly benefit efforts in controlling these diseases. Several antigens, in addition to the polysaccharide capsule, have been implicated in both the virulence and protective immunity against Streptococcus pneumoniae; one of the best-studied S. pneumoniae antigens is pneumococcal surface protein A (PspA). Recently, it was shown that genetic polymorphisms could diminish CCL5 expression, which results in increased susceptibility to and progression of infectious diseases. We previously showed CCL5 blockade reduced PspA-specific humoral and cellular pneumococcal immunity, during S. pneumoniae strain EF3030-induced carriage, by diminishing IFN-γ and enhancing IL-10 secretion by effector T cells. We also identified immuno-dominant helper T lymphocyte (HTL) epitopes in PspA peptide 19-23 (PspA199-246), which caused comparatively more cytokine secretion and proliferation responses by splenic and cervical lymph node (CLN) CD4+ T cells from mice previously challenged with S. pneumoniae strain EF3030. In this study, we sought to determine if PspA199-246–specific CD4+ T cells responses were resistant to the effect of CCL5 deficiency. In short, T cell responses against these HTL epitopes were resistant to CCL5 inhibition, than compared to cells from control or naïve mice, and unaffected by reduced co-stimulatory molecule expression caused by CCL5 blockade. CCL5 deficiency also corresponded with a higher number of IL-10+ CD11b+ CD11cLo and CD11b+ CD11cHi cells and lower IFN-γ expression by similar cells, than compared to controls. These data confirm CCL5 is an essential factor for optimal pneumococcal adaptive immunity and show CD4+ T cell responses to PspA199-246 are largely resistant to CCL5 deficiency.

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“…As a result, those DCs are not able to polarize immune response toward T helper type 1 (Th1) and cytotoxic T lymphocyte (CTL) response. (16)(17)(18)(19)(20) In that context, DCs become not only functionless, but also tolerogenic owing to their induction of T Reg cells accumulation. (21) As shown in Figure 4, incubation of imDCs with CT26-CM renders them unresponsive to immunostimulatory signal of LPS.…”

Section: Inhibition Of Ct26-cm/dc Maturationmentioning

confidence: 99%

Induction of tolerogenic dendritic cells by IL-6-secreting CT26 colon carcinoma

Alshamsan

2011

Immunopharmacology and Immunotoxicology

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One scenario by which tumors escape immune recognition is the constitutive activation of signal transducer and activator of transcription 3 (STAT3). This transcription factor mediates the production of tumor-derived factors that negatively influence target immune cells, such as dendritic cells, and polarize them toward immune-tolerance also through the induction of STAT3 activation. In the current study, the effect of p-STAT3-positive murine colon carcinoma cell line (CT26) on bone marrow-derived DCs was examined. The results showed a remarkable increase in p-STAT3 in dendritic cells (DCs) only after CT26-CM incubation. The induction of p-STAT3 in CT26-CM exposed DCs was attributed at least in part to the high levels of interleukin-6 secreted by CT26 in culture. This was also accompanied by a significant reduction in the response to the immunostimulatory adjuvant lipopolysaccharide by lowering the expression of co-stimulatory molecules CD86 and CD40. Taken together, the results suggest an inhibitory effect of CT26 colon carcinoma on DC maturation through induction of STAT3 phosphorylation. Therefore, tumor-induced p-STAT3 in DCs can be seen as a promising target for colon cancer immunotherapy.

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Co‐operative action of interleukin‐10 and interferon‐γ to regulate dendritic cell functions

Cited by 54 publications

References 44 publications

Prostaglandin E2 Potentiates Mesenchymal Stem Cell–Induced IL-10+IFN-γ+CD4+ Regulatory T Cells To Control Transplant Arteriosclerosis

Prostaglandin E2 Potentiates Mesenchymal Stem Cell–Induced IL-10+IFN-γ+CD4+ Regulatory T Cells To Control Transplant Arteriosclerosis

CCL5-independent helper T lymphocyte responses to immuno-dominant pneumococcal surface protein A epitopes

Induction of tolerogenic dendritic cells by IL-6-secreting CT26 colon carcinoma

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