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Classical dendritic cells are required for dietary antigen-mediated peripheral regulatory T cell and tolerance induction

ABSTRACT: Classical dendritic cells are required for dietary antigen-mediated peripheral regulatory T cell and tolerance induction

PROVIDER: PRJNA312191 | ENA |

REPOSITORIES: ENA

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Classical dendritic cells are required for dietary antigen-mediated peripheral regulatory T cell and tolerance induction I

Project description:Oral tolerance prevents pathological inflammatory responses towards innocuous foreign antigens via peripheral regulatory T cells (pTreg cells). However, whether a particular subset of antigen-presenting cells (APCs) is required during dietary antigen exposure to instruct naÃ¯ve CD4+ T cells to differentiate into pTreg cells has not been defined. Using myeloid lineage-specific APC depletion in mice, we found that monocyte-derived APCs are dispensable, while classical dendritic cells (cDCs) are critical for pTreg cell induction and oral tolerance. CD11bÂ¬â cDCs from the gut-draining lymph nodes efficiently induced pTreg cells, and conversely, loss of IRF8-dependent CD11bâ cDCs impaired their polarization, although oral tolerance remained intact. These data reveal the hierarchy of cDC subsets in pTreg cell induction and their redundancy during oral tolerance development. Four dendritic cell subpopulations from mouse mesenteric lymphnodes were sorted and compared in their gene expression profile

2016-03-28 | E-GEOD-77303 | biostudies-arrayexpress

Classical dendritic cells are required for dietary antigen-mediated peripheral regulatory T cell and tolerance induction II

Project description:Oral tolerance prevents pathological inflammatory responses towards innocuous foreign antigens via peripheral regulatory T cells (pTreg cells). However, whether a particular subset of antigen-presenting cells (APCs) is required during dietary antigen exposure to instruct naÃ¯ve CD4+ T cells to differentiate into pTreg cells has not been defined. Using myeloid lineage-specific APC depletion in mice, we found that monocyte-derived APCs are dispensable, while classical dendritic cells (cDCs) are critical for pTreg cell induction and oral tolerance. CD11bÂ¬â?? cDCs from the gut-draining lymph nodes efficiently induced pTreg cells, and conversely, loss of IRF8-dependent CD11bâ?? cDCs impaired their polarization, although oral tolerance remained intact. These data reveal the hierarchy of cDC subsets in pTreg cell induction and their redundancy during oral tolerance development. Sorted naÃ¯ve CD45.1 OT-II CD4 T cells were co-cultured with four dendritic cell subpopulations sorted from mouse mesenteric lymphnodes. 24h later OT-II cells were sorted again and compared in their gene expression profile.

2016-03-28 | E-GEOD-77304 | biostudies-arrayexpress

Classical dendritic cells are required for dietary antigen-mediated peripheral regulatory T cell and tolerance induction II

Project description:Oral tolerance prevents pathological inflammatory responses towards innocuous foreign antigens via peripheral regulatory T cells (pTreg cells). However, whether a particular subset of antigen-presenting cells (APCs) is required during dietary antigen exposure to instruct naïve CD4+ T cells to differentiate into pTreg cells has not been defined. Using myeloid lineage-specific APC depletion in mice, we found that monocyte-derived APCs are dispensable, while classical dendritic cells (cDCs) are critical for pTreg cell induction and oral tolerance. CD11b¬– cDCs from the gut-draining lymph nodes efficiently induced pTreg cells, and conversely, loss of IRF8-dependent CD11b– cDCs impaired their polarization, although oral tolerance remained intact. These data reveal the hierarchy of cDC subsets in pTreg cell induction and their redundancy during oral tolerance development.

2016-03-28 | GSE77304 | GEO

Classical dendritic cells are required for dietary antigen-mediated peripheral regulatory T cell and tolerance induction I

Project description:Oral tolerance prevents pathological inflammatory responses towards innocuous foreign antigens via peripheral regulatory T cells (pTreg cells). However, whether a particular subset of antigen-presenting cells (APCs) is required during dietary antigen exposure to instruct naïve CD4+ T cells to differentiate into pTreg cells has not been defined. Using myeloid lineage-specific APC depletion in mice, we found that monocyte-derived APCs are dispensable, while classical dendritic cells (cDCs) are critical for pTreg cell induction and oral tolerance. CD11b¬– cDCs from the gut-draining lymph nodes efficiently induced pTreg cells, and conversely, loss of IRF8-dependent CD11b– cDCs impaired their polarization, although oral tolerance remained intact. These data reveal the hierarchy of cDC subsets in pTreg cell induction and their redundancy during oral tolerance development.

2016-03-28 | GSE77303 | GEO

Classical dendritic cells are required for dietary antigen-mediated induction of peripheral T(reg) cells and tolerance.

Project description: Not available

| S-EPMC4837106 | biostudies-literature

Classical dendritic cells are required for dietary antigen-mediated peripheral regulatory T cell and tolerance induction

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-03-28 | E-GEOD-77305 | biostudies-arrayexpress

Classical dendritic cells are required for dietary antigen-mediated peripheral regulatory T cell and tolerance induction

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-03-28 | GSE77305 | GEO

Specialized role of migratory dendritic cells in peripheral tolerance induction.

Project description: Not available

| S-EPMC3561796 | biostudies-literature

Aire regulates transfer of antigen from mTEC to dendritic cells for induction of thymic tolerance

Project description:To investigate the role of Aire in thymic selection, we examined the cellular requirements for generation of ovalbumin (OVA)-specific CD4 and CD8 T cells in mice expressing OVA under the control of the rat insulin promoter (RIP). Aire-deficiency reduced the number of mature single positive (SP) OVA-specific CD4+ or CD8+ T cells in the thymus, independent of OVA expression. Importantly, it also contributed in two way to OVA-dependent negative selection depending on the T cell type. Aire-dependent negative selection of OVA-specific CD8 T cells correlated with Aire-regulated expression of OVA. By contrast, for OVA-specific CD4 T cells, Aire affected tolerance induction by a mechanism that operated independent of the level of OVA expression, controlling access of antigen presenting cells to mTEC-expressed OVA. This study supports the view that one mechanism by which Aire controls thymic negative selection is by regulating the indirect presentation of mTEC-derived antigens by thymic dendritic cells. It also indicates that mTEC can mediate tolerance by direct presentation of Aireregulated antigens to both CD4 and CD8 T cells. Total RNA was extracted from medullary thymic epithelial cells isolated from wildtype and Aire-deficient C57BL/6 mice for comparison of gene expression profiles.

2011-04-06 | E-GEOD-28393 | biostudies-arrayexpress

zDC (Zbtb46, Btbd4) knockout classical dendritic cells

Project description:Classical dendritic cells (cDCs) process and present antigens to T cells. Under steady-state conditions, antigen presentation by cDCs induces tolerance. In contrast, during infection or inflammation, cDCs become activated, express higher levels of cell surface MHC molecules, and induce strong adaptive immune responses. We recently identified a cDC-restricted zinc finger transcription factor, zDC, that is not expressed by other immune cell populations, including pDCs, monocytes, or macrophages. Here we define the zDC consensus DNA binding motif and the genes regulated by zDC using chromatin immunoprecipitation and deep sequencing. By deleting zDC from the mouse genome, we show that zDC is primarily a negative regulator of cDC gene expression. zDC deficiency alters the cDC subset composition in the spleen in favor of CD8+ DCs, upregulates activation pathways in steady state cDCs including elevated MHC II expression, and enhances cDC production of VEGF leading to increased vascularization of skin-draining lymph nodes. Consistent with these observations, zDC protein expression is rapidly downregulated after TLR ligation. Thus, zDC is a TLR-responsive cDC-specific transcriptional repressor that is in part responsible for preventing cDC maturation in the steady state. Splenic classical dendritic cells from mice lacking the second exon of the zDC gene were sorted. DEC-205+ and DCIR2+ cDCs from the zDC knockout mice were collected for comparison with wildtype cDCs. Three replicates per group. The wildtype samples have been previously analyzed and are available in the GEO database in Series GSE6259. The complete dataset representing: (1) the zDC knockout Samples and (2) the wildtype Samples from Series GSE6259 (re-processed using RMA), is linked below as a supplementary file.

2012-07-15 | E-GEOD-37995 | biostudies-arrayexpress

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