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Aryl hydrocarbon receptor activity downstream of IL-10 signaling is required to promote regulatory functions in human dendritic cells [RNA_in_vitro_DC10_iDC_DC10CH]

ABSTRACT: Aryl hydrocarbon receptor activity downstream of IL-10 signaling is required to promote regulatory functions in human dendritic cells [RNA_in_vitro_DC10_iDC_DC10CH]

PROVIDER: PRJNA749448 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15236423_1.fastq.gz	Fastqsanger.gz
	SRR15236423_2.fastq.gz	Fastqsanger.gz
	SRR15236424_1.fastq.gz	Fastqsanger.gz
	SRR15236424_2.fastq.gz	Fastqsanger.gz
	SRR15236425_1.fastq.gz	Fastqsanger.gz

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Aryl hydrocarbon receptor activity downstream of IL-10 signaling is required to promote regulatory functions in human dendritic cells

Project description:Aryl hydrocarbon receptor activity downstream of IL-10 signaling is required to promote regulatory functions in human dendritic cells

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Aryl hydrocarbon receptor activity downstream of IL-10 signaling is required to promote regulatory functions in human dendritic cells [RNA_ex_vivo_DC10_MS]

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Aryl hydrocarbon receptor activity downstream of IL-10 signaling is required to promote regulatory functions in human dendritic cells [ATAC_ex_vivo_DC10_cDC]

Project description:Aryl hydrocarbon receptor activity downstream of IL-10 signaling is required to promote regulatory functions in human dendritic cells [ATAC_ex_vivo_DC10_cDC]

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Aryl hydrocarbon receptor activity downstream of IL-10 signaling is required to promote regulatory functions in human dendritic cells [ATAC_in_vitro_DC10_iDC_DC10CH]

Project description:Aryl hydrocarbon receptor activity downstream of IL-10 signaling is required to promote regulatory functions in human dendritic cells [ATAC_in_vitro_DC10_iDC_DC10CH]

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Aryl hydrocarbon receptor activity downstream of IL-10 signaling is required to promote regulatory functions in human dendritic cells [RNA_in_vitro_DC10_iDC_DC10CH]

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.

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Aryl hydrocarbon receptor activity downstream of IL-10 signaling is required to promote regulatory functions in human dendritic cells [RNA_in_vitro_DC10_MS]

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Aryl hydrocarbon receptor activity downstream of IL-10 signaling is required to promote regulatory functions in human dendritic cells [RNA_ex_vivo_DC10_MS]

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Aryl hydrocarbon receptor activity downstream of IL-10 signaling is required to promote regulatory functions in human dendritic cells [ATAC_ex_vivo_DC10_cDC]

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