Similar Datasets
Project description:We used microarrays to understand the role of L-Kynurenine in inducing tolerogenic cDC2
2022-06-14 | GSE203449 | GEO
Project description:We compared migratory DCs in draining mediastinal lymph node after intranasal administration of different vaccine adjuvants based on CTA1 subunit of cholera toxin. The goal was to determine different characteristics of dendritic cells subsets after pro-inflammatory vs tolerogenic adjuvant. We had 3 groups: CTA1-DD (pro- inflammatory), CTA1(R7K)-DD (tolerogenic) and PBS to define DC which migrate to LN. All vaccine constructs included 3Ea peptide to allow for sorting of DC which took up the vaccine.
2023-05-15 | E-MTAB-12942 | biostudies-arrayexpress
Project description:Dendritic cells (DC) play critical roles in central and peripheral T cell tolerance. DC found in the steady-state periphery undergo an homeostatic, tolerogenic, maturation that promotes interaction with naive T cells and induction of abortive responses. In contrast, thymic DC are thought to exist solely in an immature state. In this study, we show that XCR1+ thymic DC constitutively mature into a stage characterized by high levels of molecules involved in T cell activation. This unanticipated mature stage corresponded to a third of the XCR1+ thymic DC and fully accounted for their ability to cross-present self-antigens to developing T cells. Transcriptomic analysis of the XCR1+ DC found in thymus and steady-state periphery revealed that their maturation involves profound and convergent changes. Unexpectedly, maturation resulted in down-regulation of genes conferring their specific function on XCR1+ DC. Paradoxically, upon maturation, central and peripheral tolerogenic XCR1+ DC up-regulated many genes thought to drive pro-inflammatory T-cell responses. Thus, our results reveal that thymic XCR1+ DC undergo constitutive maturation and emphasize the common mechanisms operating for both central and peripheral tolerance induction by XCR1+ DC. DC were isolated from lymphoid organs as previously described (Vremec et al., 2000). DC subsets were sorted by flow cytometry according to the marker combinations described in the âcharacteristics: phenotypeâ field for each sample.
2016-08-22 | E-GEOD-71166 | biostudies-arrayexpress
Project description:Background: Dendritic cells (DCs) are critical for regulating CD4 and CD8 T cell immunity, controlling Th1, Th2, and Th17 bias, generating inducible Tregs, and inducing tolerance. Multiple DC subsets have been identified in the mouse that are thought to have evolved to control these different immune outcomes. However, how these subsets differentially respond to inflammatory and/or tolerogenic signals in order to accomplish their divergent functionality remains unclear. Results: We analysed the responses of murine, splenic CD8 and CD11b DC subsets to in-vivo stimulation with lipopolysaccharide using RNA-Seq and systems biology approaches and observed responses are highly subset-specific. We reanalysed multiple datasets from the literature and show that these subset responses are obscured when analysing signaling at the population level. We show that the subset-specificity is due to the unique regulation of distinct TLR4 pathway modulators that ‘fine-tune’ a common TLR4 cascade rather and not due to major differences in signaling pathways or transcription factors. Conclusions: We propose the Pathway Modulation Model wherein common signaling pathways are regulated by unique sets of modulators allowing for distinct immune responses in closely related DC subsets. We extend these observations using analagous datasets from the literature and show that our model provides a global mechanism for generating cell subset-specific signaling in multiple subpopulations in mouse and man. Splenic CD8 and CD11b DC subsets from LPS stimulated (10 pooled animals) and Control (5 pooled animals) mice were analysed by RNA-Seq.
2014-07-01 | E-GEOD-42573 | biostudies-arrayexpress
Project description:Dendritic cell (DC) activation and function are underpinned by profound changes in cellular metabolism. Several studies indicate that the ability of DCs to promote tolerance is dependent on catabolic metabolism. Yet the contribution of AMP-activated kinase (AMPK), a central energy sensor promoting catabolism, to DC tolerogenicity remains unknown. Here, we show that AMPK activation renders human monocyte-derived DCs tolerogenic as evidenced by an enhanced ability to drive differentiation of regulatory T cells, a process dependent on increased RALDH activity. This is accompanied by a several metabolic changes, including increased breakdown of glycerophospholipids, enhanced mitochondrial fission-dependent fatty acid oxidation, and upregulated glucose catabolism. This metabolic rewiring is functionally important as we found interference with these metabolic processes to reduce to various degrees AMPK-induced RALDH activity as well as the tolerogenic capacity of moDCs. Altogether, our findings reveal a key role for AMPK signaling in shaping DC tolerogenicity, and suggest AMPK as target to direct DC-driven tolerogenic responses in therapeutic settings.
2024-07-16 | PXD053979 | Pride
Project description:Transcriptional profiling of human dendritic cells (DC) comparing control (DC generated with GM-CSF plus IL-4) with three different treatments of tolerogenic (DC generated with GM-CSF plus IL-4 and IL-10, or IL-4, IL-10, and IL-6, or IL-4, IL-10, and TGF-b1) Three two-condition experiments, control (N) vs tolerogenic DC with three different treatments. Pool of 4 indivuduals for each condition. One replicate per array.
2009-11-12 | E-GEOD-18921 | biostudies-arrayexpress
Project description:We use tolDCs from syngeneic (C57BL6) and allogeneic (BALB/c) mice to show potent renoprotective abilities in a ischemia reperfusion AKI model. Dendritic cells were derived from mice bone marrow and cultured for 7 days with GM-CSF and IL-4. Tolerogenic DCs were cultured in the same DC media but with the addition of VitD3 and IL10. LPS was added on day 6 and cells harvested for use or analysis on day 7.
2023-07-01 | GSE205322 | GEO
Project description:Peripheral immune tolerance is a key physiological mechanism sustained by the activity of regulatory cells that impedes immune reaction to self and non-dangerous antigens. Interleukin 10 (IL-10) plays a key immunosuppressive role in this system by inhibiting effector cells and instructing regulatory cells. While the molecular mechanisms and gene expression patterns defining identity and function of T regulatory cells have been deeply studied, the molecular pattern driving tolerogenicity in myeloid antigen presenting cells remain less defined. We have investigated the molecular mechanisms underlying IL-10 tolerogenic activity in human myeloid cells. By performing chromatin and transcriptomic studies in IL-10-induced monocyte-derived DC, we have found that IL-10 imprinted a pattern of accessible enhancers, which were exploited by Aryl Hydrocarbon Receptor (AHR) to promote the expression of a set of core genes. Functional studies demonstrated that AHR activation and core gene expression were necessary for IL-10-mediated induction of tolerogenic functions in in vitro differentiated DC. AHR exerted its role down-stream to IL-10 inducing tolerogenic and repressing inflammatory genes. Analyses of naturally occurring tolerogenic DC from peripheral blood showed that the IL-10-induced AHR module was active also in vivo in healthy conditions. In multiple sclerosis patients, instead, we observed significant alterations in the IL-10-induced AHR module that correlated with functional defects and reduced frequencies of in vitro differentiated and in vivo occurring IL-10-induced tolerogenic DC, respectively. This study unveiled a previously undescribed IL-10-induced molecular mechanism required for establishing tolerogenic functions in human myeloid cells.
2023-03-04 | GSE180754 | GEO
Project description:Peripheral immune tolerance is a key physiological mechanism sustained by the activity of regulatory cells that impedes immune reaction to self and non-dangerous antigens. Interleukin 10 (IL-10) plays a key immunosuppressive role in this system by inhibiting effector cells and instructing regulatory cells. While the molecular mechanisms and gene expression patterns defining identity and function of T regulatory cells have been deeply studied, the molecular pattern driving tolerogenicity in myeloid antigen presenting cells remain less defined. We have investigated the molecular mechanisms underlying IL-10 tolerogenic activity in human myeloid cells. By performing chromatin and transcriptomic studies in IL-10-induced monocyte-derived DC, we have found that IL-10 imprinted a pattern of accessible enhancers, which were exploited by Aryl Hydrocarbon Receptor (AHR) to promote the expression of a set of core genes. Functional studies demonstrated that AHR activation and core gene expression were necessary for IL-10-mediated induction of tolerogenic functions in in vitro differentiated DC. AHR exerted its role down-stream to IL-10 inducing tolerogenic and repressing inflammatory genes. Analyses of naturally occurring tolerogenic DC from peripheral blood showed that the IL-10-induced AHR module was active also in vivo in healthy conditions. In multiple sclerosis patients, instead, we observed significant alterations in the IL-10-induced AHR module that correlated with functional defects and reduced frequencies of in vitro differentiated and in vivo occurring IL-10-induced tolerogenic DC, respectively. This study unveiled a previously undescribed IL-10-induced molecular mechanism required for establishing tolerogenic functions in human myeloid cells.
2023-03-04 | GSE180761 | GEO
Project description:Peripheral immune tolerance is a key physiological mechanism sustained by the activity of regulatory cells that impedes immune reaction to self and non-dangerous antigens. Interleukin 10 (IL-10) plays a key immunosuppressive role in this system by inhibiting effector cells and instructing regulatory cells. While the molecular mechanisms and gene expression patterns defining identity and function of T regulatory cells have been deeply studied, the molecular pattern driving tolerogenicity in myeloid antigen presenting cells remain less defined. We have investigated the molecular mechanisms underlying IL-10 tolerogenic activity in human myeloid cells. By performing chromatin and transcriptomic studies in IL-10-induced monocyte-derived DC, we have found that IL-10 imprinted a pattern of accessible enhancers, which were exploited by Aryl Hydrocarbon Receptor (AHR) to promote the expression of a set of core genes. Functional studies demonstrated that AHR activation and core gene expression were necessary for IL-10-mediated induction of tolerogenic functions in in vitro differentiated DC. AHR exerted its role down-stream to IL-10 inducing tolerogenic and repressing inflammatory genes. Analyses of naturally occurring tolerogenic DC from peripheral blood showed that the IL-10-induced AHR module was active also in vivo in healthy conditions. In multiple sclerosis patients, instead, we observed significant alterations in the IL-10-induced AHR module that correlated with functional defects and reduced frequencies of in vitro differentiated and in vivo occurring IL-10-induced tolerogenic DC, respectively. This study unveiled a previously undescribed IL-10-induced molecular mechanism required for establishing tolerogenic functions in human myeloid cells.
2023-03-04 | GSE180760 | GEO