Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA356877 | ENA |
REPOSITORIES: ENA
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Project description:We have identified the dendritic cell (DC) populations that are sufficient for the induction of T helper 2 (Th2) cell responses in the intestine against both live Trichuris muris worms, and inert Schistosoma mansoni eggs. Antigen-specific Th2 responses did not develop after deletion of IRF4 in DCs, yet IRF4-deficient DCs were not functionally affected. Instead, IRF4flox/flox CD11c-cre mice had fewer CD11b+ migrating DCs, and fewer DCs carrying parasite antigen from the intestine. Adoptive transfer of purified DCs from infected animals directly into intestinal afferent lymphatics enabled us to identify that CD11b+CD103+ DCs were central to the induction of Th2 responses in the small intestine, whereas CD11b+CD103- DCs were more important in the colon. Similarly, after pulsing with Schistosome egg antigen (SEA) in vitro, adoptively-transferred small intestinal or colonic DCs acquired the ability to induce SEA-specific Th2 responses. These data demonstrate a functional specialisation among intestinal DC populations in inducing Th2 responses, and elucidate the roles of IRF4 in this process.
2016-12-10 | GSE91381 | GEO
Project description:Subset-specific and progenitor gene expression analysis of Klf4+/+ and Klf4-/- DCs. The two major lineages of classical dendritic cells (cDCs) express and require either IRF8 or IRF4 transcription factors for their development and function. IRF8-dependent cDCs promote anti-viral and T-helper 1 (Th1) cell responses, whereas IRF4-expressing cDCs have been implicated in controlling both Th2 and Th17 cell responses. Here, we have provided evidence that Kruppel-like factor 4 (Klf4) is required in IRF4-expressing cDCs to promote Th2 but not Th17 cell responses in vivo. Conditional Klf4 deletion within cDCs impaired Th2 cell responses during Schistosoma mansoni infection, Schistosoma egg antigen (SEA) immunization, and house dust mite challenge (HDM), without affecting cytotoxic T lymphocyte (CTL), Th1 and Th17 cell responses to herpes simplex virus, Toxoplasma gondii and Citrobacter rodentium infections. Further, Klf4 deletion reduced IRF4 expression in pre-cDCs and resulted in selective loss of IRF4-expressing cDCs subsets in several tissues. These results indicate that Klf4 guides a transcriptional program promoting IRF4-expressing cDCs heterogeneity. Bone marrow progenitors and skin draining LN subsets were harvested from 4 Klf4fl/fl cre negative or Vav1-icre mice and were sorted to >95% purity on the FACS Aria 3.
2015-05-19 | E-GEOD-68590 | biostudies-arrayexpress
Project description:Lung-resident conventional dendritic cells (cDCs) coordinate immune responses to respiratory viruses in the respiratory tract or after migration to mediastinal lymph nodes (mLN). Migratory DCs include cDC1s (CD103+XCR1+CD24hi) expressing IRF8 or cDC2s (CD11b+SIRPa+CD24+) expressing IRF4. IRF4+ cDC2s are divided into a CD24hi subset that requires IRF4 for differentiation and a CD24int subset that is present in the absence of IRF4. During influenza A virus (IAV) infection of mice, we characterized the kinetics of cDC2 subset accumulation in the lung and mLN and their differences in IRF4-dependent gene expression and function. We found that the two IRF4-expressing cDC2 subsets upregulated CD86 to high levels, produced IL-12p40 and the chemokines CCL17 and CCL2, and were capable of acquiring antigen in vivo and activating antigen-specific CD8+ T cells. Notably, the CD11b+CD24int cDC2 subset expressed canonical cDC markers and transcription factors and expanded to high numbers in the lung and mLN by day 6 post-infection. Transcriptome analyses on day 5 post-infection revealed that the CD11b+CD24int cDC2 subset expressed both IRF4 and IRF8 and harbored an elevated interferon response signature compared to the CD11b+CD24hi subset. Analyses of mice lacking Irf4 in CD11c+ cells showed that IRF4 promoted the function of CD11b+CD24int cDC2s, including the capacity to migrate to mLN and to produce CCL17 and CCL22, consistent with their altered gene expression profile in the absence of IRF4. In sum, our data show that the two lung-resident CD11b+ cDC2 subsets present in naïve mice elaborated distinct and common functional responses regulated by IRF4 during IAV infection.
2025-01-31 | GSE285970 | GEO
Project description:Dendritic cells (DCs) in tissues and lymphoid organs comprise distinct functional subsets that differentiate in situ from circulating progenitors. Tissue-specific signals that regulate DC subset differentiation are poorly understood. We report that DC-specific deletion of the Notch2 receptor caused a reduction of DC populations in the spleen. Within the splenic CD11b+ DCs, Notch signaling blockade ablated a distinct population marked by high expression of adhesion molecule Esam. The Notch-dependent Esamhi DC subset also required lymphotoxin beta receptor signaling, proliferated in situ and facilitated efficient CD4+ T cell priming. The Notch-independent Esamlo DCs expressed monocyte-related genes and showed superior cytokine responses. In addition, Notch2 deletion led to the loss of CD11b+ CD103+ DCs in the intestinal lamina propria and to the corresponding decrease of IL-17-producing CD4+ T cells in the intestine. Thus,Notch2 is a common differentiation signal for T cell-priming CD11b+ DC subsets in the spleen and intestine.
2011-10-31 | GSE31551 | GEO
Project description:Subset-specific and progenitor gene expression analysis of Klf4+/+ and Klf4-/- DCs. The two major lineages of classical dendritic cells (cDCs) express and require either IRF8 or IRF4 transcription factors for their development and function. IRF8-dependent cDCs promote anti-viral and T-helper 1 (Th1) cell responses, whereas IRF4-expressing cDCs have been implicated in controlling both Th2 and Th17 cell responses. Here, we have provided evidence that Kruppel-like factor 4 (Klf4) is required in IRF4-expressing cDCs to promote Th2 but not Th17 cell responses in vivo. Conditional Klf4 deletion within cDCs impaired Th2 cell responses during Schistosoma mansoni infection, Schistosoma egg antigen (SEA) immunization, and house dust mite challenge (HDM), without affecting cytotoxic T lymphocyte (CTL), Th1 and Th17 cell responses to herpes simplex virus, Toxoplasma gondii and Citrobacter rodentium infections. Further, Klf4 deletion reduced IRF4 expression in pre-cDCs and resulted in selective loss of IRF4-expressing cDCs subsets in several tissues. These results indicate that Klf4 guides a transcriptional program promoting IRF4-expressing cDCs heterogeneity.
2015-05-19 | GSE68590 | GEO
Project description:Dendritic cells (DCs) in tissues and lymphoid organs comprise distinct functional subsets that differentiate in situ from circulating progenitors. Tissue-specific signals that regulate DC subset differentiation are poorly understood. We report that DC-specific deletion of the Notch2 receptor caused a reduction of DC populations in the spleen. Within the splenic CD11b+ DCs, Notch signaling blockade ablated a distinct population marked by high expression of adhesion molecule Esam. The Notch-dependent Esamhi DC subset also required lymphotoxin beta receptor signaling, proliferated in situ and facilitated efficient CD4+ T cell priming. The Notch-independent Esamlo DCs expressed monocyte-related genes and showed superior cytokine responses. In addition, Notch2 deletion led to the loss of CD11b+ CD103+ DCs in the intestinal lamina propria and to the corresponding decrease of IL-17-producing CD4+ T cells in the intestine. Thus,Notch2 is a common differentiation signal for T cell-priming CD11b+ DC subsets in the spleen and intestine. We compared genome-wide expression profiles of wild-type Esam(hi) and Esam(lo) splenic CD11b+ DC populations, along with CD11b+ DCs from DC-RBPJΔ mice. Spleens from 2-3 Cx3cr1-GFP+ RBPJflox/flox CD11c-Cre+ mice or Cx3cr1-GFP+ RBPJflox/flox Cre-negative littermate controls were isolated, pooled and depleted of lymphoid and erythroid cells by negative selection on MACS columns. Live cells were stained for surface expression of CD11c, CD11b and Esam. CD11c(hi) CD11b+ DCs from control mice could be separated into Esam(lo) GFP(hi) versus Esam(hi) GFP(lo) subsets. CD11c(hi) CD11b+ DCs from RBPJ-targeted mice spleens were uniformly Esam(lo) GFP(hi). The two subsets from control mice and single Esam(lo) GFP(hi) subset from RBPJ-targeted mice were sorted using FACSAria II flow sorter and analyzed using GeneChip Mouse Gene 1.0 ST Array (Affymetrix).
2011-10-31 | E-GEOD-31551 | biostudies-arrayexpress
Project description:Dendritic cell (DC) are critical initiators and regulators of immunity to pathogens, vaccines, tumors and tolerance to self. Mouse and human dendritic cells (DCs) are comprised of functionally specialized subsets, but precise interspecies correlation is currently incomplete and hampers the full translation of murine findings to human DC-based clinical therapies. In this study, we show that murine lung and gut lamina propria CD11b+ DC populations are comprised of two subsets: FLT3- and IRF4-dependent CD24+CD64- DCs and contaminating CSF-1R-dependent CD24-CD64+ macrophages. CD11b+CD24+CD64- DCs are instrumental in inducing Th17 cell immune response in the steady state and upon Aspergillus fumigatus challenge. We also identified human CD1c+CD11b+ DCs as the functional homologue of mouse mucosal CD11b+ DCs. Our findings highlight the conservation of key immune functions across species and aid the translation of murine studies to human DC immunobiology. The data for the associated human studies have been stored within GSE35459. Gene Expression from total RNA from specific mouse dendritic cell subsets purified by FACS
2013-05-29 | E-GEOD-46680 | biostudies-arrayexpress
Project description:Using mouse lung resident conventional CD11b+ dendritic cells (CD11b+ cDCs) in the context of house-dust mite (HDM)-driven allergic airway sensitization as a model, we aimed here to identify transcriptional events regulating the pro-Th2 activity of cDCs. We used microarray analyses to identify genes differentially expressed by lung CD11b+ conventional dendritic cells in response to house dust mite allergens in wild-type and Irf3-deficient mice
2016-09-30 | GSE80809 | GEO
Project description:CD11b+ cell populations, especially macrophages are highly heterogeneous tissue resident immune cells in both mice and human. Exact subsets and their phenotype remain unknown. We here analyzed gut CD11b+ cell populations using scRNA-seq in normal, inflamed and Nlrc4 deficient mice. There existed twelve CD11b+ cell populations and subsets in SPF mice. These CD11b+ subsets were changeable dependent on inflammation and gut environment. We found consistent high expression of Ly6C, Cd62L, previously undescribed Trem1 and Ccr7 in Ly6Chigh macrophages and Cd206 and Cx3cr1 in Ly6Clow/neg cell population in different mice. However, signature genes showed that resident macrophages but not inflammatory macrophages were highly conserved in normal and inflamed mice. Gut microbiota play a role in accumulation and differentiation of gut macrophages. Both Ly6Chigh and Ly6Clow macrophages in intestine and colon tissues are similar. These uncover the transcriptional landscape and phenotypic heterogeneity of CD11b+ cells, especially macrophages in gut tissues.
2019-10-16 | GSE138902 | GEO
Project description:Dendritic cell (DC) are critical initiators and regulators of immunity to pathogens, vaccines, tumors and tolerance to self. Mouse and human dendritic cells (DCs) are comprised of functionally specialized subsets, but precise interspecies correlation is currently incomplete and hampers the full translation of murine findings to human DC-based clinical therapies. In this study, we show that murine lung and gut lamina propria CD11b+ DC populations are comprised of two subsets: FLT3- and IRF4-dependent CD24+CD64- DCs and contaminating CSF-1R-dependent CD24-CD64+ macrophages. CD11b+CD24+CD64- DCs are instrumental in inducing Th17 cell immune response in the steady state and upon Aspergillus fumigatus challenge. We also identified human CD1c+CD11b+ DCs as the functional homologue of mouse mucosal CD11b+ DCs. Our findings highlight the conservation of key immune functions across species and aid the translation of murine studies to human DC immunobiology. The data for the associated human studies have been stored within GSE35459.
2013-05-29 | GSE46680 | GEO