Project description:We deciphered the transcriptional landscape of Peyer's patch CD11c+ phagocytes from their emergence in the tissue to their final maturation state at homeostasis and under stimulation with the TLR7 ligand R848 and the TLR9 ligand CpG.
Project description:The initiation of the mucosal immune response in Peyer’s patch (PP) relies on the sampling, processing and efficient presentation of foreign antigens by dendritic cells (DC). PP DC encompass five subsets, among which CD11b+ conventional DC (cDC) and LysoDC have distinct progenitors and functions but share many cell surface markers. This has previously led to confusion between these two subsets. In addition, another PP DC subset, termed double-negative (DN), remains poorly characterized. Here, we have studied the genetic relatedness of the different subsets of PP cDC at steady state and under TLR7 ligand stimulation. We also provide the transcriptional profiles of subepithelial TIM-4- and interfollicular TIM-4+ macrophages.
Project description:Gene expression data of Peyer's patch LysoDC differentiation states and macrophages at steady state and under TLR7 ligand stimulation
Project description:PeyerM-bM-^@M-^Ys patches (PP) are primary inductive sites of mucosal immunity. Defining PP mononuclear phagocyte system (MPS) is thus crucial to understand the initiation of mucosal immune response. We provide a comprehensive analysis of the phenotype, distribution, ontogeny, lifespan, function and transcriptional profile of PP MPS. We show that monocytes give rise to macrophages and to lysozyme-expressing DC (LysoDC) which are both involved in particulate antigen uptake, display strong innate antiviral and antibacterial gene signatures and, upon TLR7 stimulation, secrete IL-6 and TNF but no IL-10. However, unlike macrophages, LysoDC display a rapid renewal rate, strongly express genes of the MHCII presentation pathway and prime naM-CM-/ve helper T cells for IFNg production. Our results show that in PP, at steady state, monocytes generate both LysoDC and macrophages which display distinct features from their adjacent villus counterparts. 3 replicates of 3 different mononuclear phagocyte subsets have been extracted from Peyer's Patches of WT C57Bl/6 mice: CD11b+ DC, lysoDC and lysoMac. The total RNA of PP-sorted cells from the 3 independent experiments was extracted with a Qiagen micro RNAeasy PLUS kit. Quantity, quality and absence of genomic DNA contamination were assessed with a Bioanalyser (Agilent). Microarray experiments were performed by the Plateforme Biopuces of Strasbourg (France) using the GeneChipM-BM-. Mouse Gene 1.0 ST array.
Project description:Dendritic cells (DC) facilitate the maintenance of immunological tolerance in the steady state. We report that transcription factor Etv3 is preferentially expressed in mature DC including tissue-derived migratory DC (migDC), and facilitates their homeostatic maturation and CCR7-dependent migration. Mice with global or DC-specific deletion of Etv3 manifested the expansion of CD25low regulatory T cells (Treg), spontaneous activation of conventional T cells, and multiorgan T cell infiltration. Etv3 deficiency exacerbated TLR7-driven systemic lupus erythematosus (SLE)-like disease, supporting the reported genetic association of human ETV3 with SLE. Etv3-deficient migDC upregulated multiple costimulatory molecules including OX40 ligand (OX40L/TNFSF4), whose blockade partially rescued the Treg abnormalities. These results identify Etv3 as an essential regulator of the tolerogenic function of DC, and implicate it in the regulation of human autoimmunity.
Project description:Dendritic cells (DC) facilitate the maintenance of immunological tolerance in the steady state. We report that transcription factor Etv3 is preferentially expressed in mature DC including tissue-derived migratory DC (migDC), and facilitates their homeostatic maturation and CCR7-dependent migration. Mice with global or DC-specific deletion of Etv3 manifested the expansion of CD25low regulatory T cells (Treg), spontaneous activation of conventional T cells, and multiorgan T cell infiltration. Etv3 deficiency exacerbated TLR7-driven systemic lupus erythematosus (SLE)-like disease, supporting the reported genetic association of human ETV3 with SLE. Etv3-deficient migDC upregulated multiple costimulatory molecules including OX40 ligand (OX40L/TNFSF4), whose blockade partially rescued the Treg abnormalities. These results identify Etv3 as an essential regulator of the tolerogenic function of DC, and implicate it in the regulation of human autoimmunity.
Project description:Dendritic cells (DC) facilitate the maintenance of immunological tolerance in the steady state. We report that transcription factor Etv3 is preferentially expressed in mature DC including tissue-derived migratory DC (migDC), and facilitates their homeostatic maturation and CCR7-dependent migration. Mice with global or DC-specific deletion of Etv3 manifested the expansion of CD25low regulatory T cells (Treg), spontaneous activation of conventional T cells, and multiorgan T cell infiltration. Etv3 deficiency exacerbated TLR7-driven systemic lupus erythematosus (SLE)-like disease, supporting the reported genetic association of human ETV3 with SLE. Etv3-deficient migDC upregulated multiple costimulatory molecules including OX40 ligand (OX40L/TNFSF4), whose blockade partially rescued the Treg abnormalities. These results identify Etv3 as an essential regulator of the tolerogenic function of DC, and implicate it in the regulation of human autoimmunity.
Project description:Dendritic cells (DC) facilitate the maintenance of immunological tolerance in the steady state. We report that transcription factor Etv3 is preferentially expressed in mature DC including tissue-derived migratory DC (migDC), and facilitates their homeostatic maturation and CCR7-dependent migration. Mice with global or DC-specific deletion of Etv3 manifested the expansion of CD25low regulatory T cells (Treg), spontaneous activation of conventional T cells, and multiorgan T cell infiltration. Etv3 deficiency exacerbated TLR7-driven systemic lupus erythematosus (SLE)-like disease, supporting the reported genetic association of human ETV3 with SLE. Etv3-deficient migDC upregulated multiple costimulatory molecules including OX40 ligand (OX40L/TNFSF4), whose blockade partially rescued the Treg abnormalities. These results identify Etv3 as an essential regulator of the tolerogenic function of DC, and implicate it in the regulation of human autoimmunity.
Project description:Dendritic cells (DC) facilitate the maintenance of immunological tolerance in the steady state. We report that transcription factor Etv3 is preferentially expressed in mature DC including tissue-derived migratory DC (migDC), and facilitates their homeostatic maturation and CCR7-dependent migration. Mice with global or DC-specific deletion of Etv3 manifested the expansion of CD25low regulatory T cells (Treg), spontaneous activation of conventional T cells, and multiorgan T cell infiltration. Etv3 deficiency exacerbated TLR7-driven systemic lupus erythematosus (SLE)-like disease, supporting the reported genetic association of human ETV3 with SLE. Etv3-deficient migDC upregulated multiple costimulatory molecules including OX40 ligand (OX40L/TNFSF4), whose blockade partially rescued the Treg abnormalities. These results identify Etv3 as an essential regulator of the tolerogenic function of DC, and implicate it in the regulation of human autoimmunity.
Project description:Dendritic cells (DC) facilitate the maintenance of immunological tolerance in the steady state. We report that transcription factor Etv3 is preferentially expressed in mature DC including tissue-derived migratory DC (migDC), and facilitates their homeostatic maturation and CCR7-dependent migration. Mice with global or DC-specific deletion of Etv3 manifested the expansion of CD25low regulatory T cells (Treg), spontaneous activation of conventional T cells, and multiorgan T cell infiltration. Etv3 deficiency exacerbated TLR7-driven systemic lupus erythematosus (SLE)-like disease, supporting the reported genetic association of human ETV3 with SLE. Etv3-deficient migDC upregulated multiple costimulatory molecules including OX40 ligand (OX40L/TNFSF4), whose blockade partially rescued the Treg abnormalities. These results identify Etv3 as an essential regulator of the tolerogenic function of DC, and implicate it in the regulation of human autoimmunity.