Sequential Role of Plasmacytoid Dendritic Cells and Regulatory T Cells in Oral Tolerance

Dubois, Bertrand; Joubert, Grégoire; Agüero, Mercedes Gomez de; Gouanvic, Marie; Goubier, Anne; Kaiserlian, Dominique

doi:10.1053/j.gastro.2009.03.055

Cited by 78 publications

(80 citation statements)

References 29 publications

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“…One explanation for this surprising observation might be enhanced consumption of IFN-a during naive T-cell differentiation by MLN pDC, which cannot be excluded but seems unlikely in the absence of supporting differences in our co-culture experiments. On the other hand, IFN-a production might be down-regulated in MLN pDC by rendered TLR7 or TLR9 27 signalling, which involves the interferon regulatory factors 5 and 7. 51 (Over)production of IFN-a by pDC has been shown to be critical for disease progression in human psoriasis and systemic lupus erythematosus 52 and inhibition of IFN-a in a xenograft model of murine psoriasis could inhibit the T-cell-dependent disease progression.…”

Section: Discussionmentioning

confidence: 99%

“…25,26 Recent data from murine models indicate a possible role of pDC in oral tolerance apart from that of mDC. [27][28][29][30] In humans, IL-10-producing Foxp-3 + CD4 + CD25 + regulatory T cells can be induced by TLR9-activated pDC obtained from PB. 31 The MLN compartment appears to be crucial for the observed dysregulation of T helper type 1/type 17 responses in IBD 32 but a precise characterization of human MLN pDC is missing.…”

Section: M M U N O L O G Y O R I G I N a L A R T I C L Ementioning

confidence: 99%

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Dendritic cells from human mesenteric lymph nodes in inflammatory and non‐inflammatory bowel diseases: subsets and function of plasmacytoid dendritic cells

et al. 2013

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SummaryPlasmacytoid dendritic cells (pDC) in mesenteric lymph nodes (MLN) may be important regulators of both inflammatory and non-inflammatory mucosal immune responses but human studies are rare. Here we compare pDC from human MLN and peripheral blood (PB) by phenotype and function. MLN from patients with or without inflammatory bowel disease (IBD) undergoing colon surgery and PB from patients with IBD and from controls were used to isolate mononuclear cells. The pDC were analysed by flow cytometry for the expression of CD40, CD80, CD83, CD86, CCR6, CCR7, CX3CR1, CD103 and HLA-DR. Purified pDC from MLN and PB were stimulated with staphylococcus enterotoxin B (SEB), CpG-A, interleukin-3 (IL-3), SEB + IL-3, CpG-A + IL-3 or left unstimulated, and cultured alone or with purified allogeneic CD4 + CD45RA + HLA-DR-T cells. Subsequently, concentrations of IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, interferon-a (IFN-a), IFN-c and tumour necrosis factor-a (TNF-a) in culture supernatants were determined by multiplex bead array. The PB pDC from IBD patients exhibited an activated and matured phenotype whereas MLN pDC and control PB pDC were less activated. CpG-A and CpG-A + IL-3-stimulated MLN pDC secreted less IL-6 and TNF-a compared with PB pDC from controls. Compared with co-cultures of naive CD4 T cells with PB pDC, co-cultures with MLN pDC contained more IL-2, IL-10 and IFN-c when stimulated with SEB and SEB + IL-3, and less IFN-a when stimulated with CpG-A. MLN pDC differ phenotypically from PB pDC and their pattern of cytokine secretion and may contribute to specific outcomes of mucosal immune reactions.

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Section: Discussionmentioning

confidence: 99%

Section: M M U N O L O G Y O R I G I N a L A R T I C L Ementioning

confidence: 99%

Dendritic cells from human mesenteric lymph nodes in inflammatory and non‐inflammatory bowel diseases: subsets and function of plasmacytoid dendritic cells

et al. 2013

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“…Our study thus assigns a critical role to epidermal LCs in protection from development of T cell-mediated cutaneous allergies to the weak sensitizer DNTB and identifies 2 complementary pathways of skin tolerance that are reminiscent of those described for orally induced tolerance (35,48). The exact molecular mechanisms by which LCs induce anergy/deletion of allergen-specific CD8 + T cells and activation/expansion of ICOS + Tregs remain to be characterized and will require further in-depth investigations.…”

Section: Cd207 -Ddcs To Lnsmentioning

confidence: 99%

Langerhans cells protect from allergic contact dermatitis in mice by tolerizing CD8+ T cells and activating Foxp3+ regulatory T cells

Vocanson²,

et al. 2012

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Allergic contact dermatitis is the most frequent occupational disease in industrialized countries. It is caused by CD8 + T cell-mediated contact hypersensitivity (CHS) reactions triggered at the site of contact by a variety of chemicals, also known as weak haptens, present in fragrances, dyes, metals, preservatives, and drugs. Despite the myriad of potentially allergenic substances that can penetrate the skin, sensitization is relatively rare and immune tolerance to the substance is often induced by as yet poorly understood mechanisms. Here we show, using the innocuous chemical 2,4-dinitrothiocyanobenzene (DNTB), that cutaneous immune tolerance in mice critically depends on epidermal Langerhans cells (LCs), which capture DNTB and migrate to lymph nodes for direct presentation to CD8 + T cells. Depletion and adoptive transfer experiments revealed that LCs conferred protection from development of CHS by a mechanism involving both anergy and deletion of allergen-specific CD8 + T cells and activation of a population of T cells identified as ICOS + CD4 + Foxp3 + Tregs. Our findings highlight the critical role of LCs in tolerance induction in mice to the prototype innocuous hapten DNTB and suggest that strategies targeting LCs might be valuable for prevention of cutaneous allergy.

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“…Oral tolerance is a physiological mechanism, which prevents hypersensitivity reactions to dietary antigens and we have previously reported that it is mediated by CD4+CD25+ regulatory T cells (Treg) [3,4,5]. Treg comprise several subsets including, naturally occurring and thymus-derived CD4+CD25+ Treg expressing the transcription factor Foxp3 as well as antigen-induced CD4+CD25+Foxp3+ Treg, IL-10-producing (Tr1) and TGF-β-producing (Th3) Treg cells generated in the periphery, which suppress CD4+ and CD8+ T cell responses and can control inflammatory and autoimmune diseases [6].…”

Section: Introductionmentioning

confidence: 99%

Regulatory T Cells Control Type I Food Allergy to Beta-Lactoglobulin in Mice

Kanjarawi¹,

Dercamp²,

Etchart³

et al. 2011

Int Arch Allergy Immunol

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Background: Regulatory T cells contribute to peripheral immune tolerance, yet their ability to control immediate-type hypersensitivity (ITH) reactions involved in IgE-mediated food allergy is still poorly documented. Objectives: We investigated in mice whether CD4+CD25+ regulatory T cells could control ITH to β-lactoglobulin (BLG), a major allergen in cow’s milk. Methods: C3H/HeOuJ mice were sensitized by repeated oral gavage with BLG plus cholera toxin as adjuvant and orally challenged with BLG alone to elicit allergic symptoms. Mice were treated with the anti-CD25 mAb (PC61) before sensitization. Oral sensitization (afferent phase of ITH) was assessed by production of BLG-specific serum antibodies and Th1/Th2-type cytokines by specific CD4+ T cells in mesenteric lymph nodes. ITH was elicited by oral BLG challenge (efferent phase of ITH) and we monitored symptom scores, numbers and function of intestinal mast cells and serum level of the mucosal mast cell protease mMCP-1. Results: Upon oral BLG challenge, orally sensitized mice developed only mild clinical signs. Anti-CD25 mAb-treated mice exhibited enhancement of both BLG-specific CD4+ T cell priming with IL-4, IL-5, IL-13 and IFN-γ production and total IgE, and BLG-specific IgE, IgG1 and IgG2a in serum. Anti-CD25 mAb treatment caused more severe symptoms upon BLG challenge, which correlated with enhanced serum levels of the mucosal mast cell protease mMCP-1. Conclusions: These data document that constitutive CD4+CD25+ regulatory T cells alleviate clinical signs of ITH to dietary BLG by modulating the priming of BLG-specific T and B cell responses during oral sensitization and enhancing mast cell degranulation.

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Sequential Role of Plasmacytoid Dendritic Cells and Regulatory T Cells in Oral Tolerance

Cited by 78 publications

References 29 publications

Dendritic cells from human mesenteric lymph nodes in inflammatory and non‐inflammatory bowel diseases: subsets and function of plasmacytoid dendritic cells

Dendritic cells from human mesenteric lymph nodes in inflammatory and non‐inflammatory bowel diseases: subsets and function of plasmacytoid dendritic cells

Langerhans cells protect from allergic contact dermatitis in mice by tolerizing CD8+ T cells and activating Foxp3+ regulatory T cells

Regulatory T Cells Control Type I Food Allergy to Beta-Lactoglobulin in Mice

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