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Transcriptional and Functional Programming of Decidual Innate Lymphoid Cells

ABSTRACT: Transcriptional and Functional Programming of Decidual Innate Lymphoid Cells

PROVIDER: PRJNA531718 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8872350_1.fastq.gz	Fastqsanger.gz
	SRR8872350_2.fastq.gz	Fastqsanger.gz
	SRR8872351_1.fastq.gz	Fastqsanger.gz
	SRR8872351_2.fastq.gz	Fastqsanger.gz
	SRR8872352_1.fastq.gz	Fastqsanger.gz

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Transcriptional and Functional Programming of Decidual Innate Lymphoid Cells

Project description:A successful pregnancy requires many physiological adaptations from the mother, including the establishment of tolerance towards the semiallogeneic fetus. Innate lymphoid cells (ILCs) have arisen as important players in immune regulation and tissue homeostasis at mucosal and barrier surfaces. Dimensionality reduction and transcriptomic analysis revealed the presence of two novel CD56Bright decidual ILCs, C10 and C2, that express divergent levels of Eomes. We found that decidual C10, C2, and cNKs correlated highly with previously identified first trimester decidual dNKs (dNK1-3). Functional analysis revealed polyfunctional profiles that depend on the nature of the stimulus, with a preference for IFNgamma and VEGF production. Overall, our data suggests persistence of pregnancy-specific decidual innate lymphocytes across pregnancy.

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Transcriptional and Functional Programming of Decidual Innate Lymphoid Cells.

Project description:A successful pregnancy requires many physiological adaptations from the mother, including the establishment of tolerance toward the semiallogeneic fetus. Innate lymphoid cells (ILCs) have arisen as important players in immune regulation and tissue homeostasis at mucosal and barrier surfaces. Dimensionality reduction and transcriptomic analysis revealed the presence of two novel CD56Bright decidual ILCs that express low T-bet and divergent Eomes levels. Transcriptional correlation with recently identified first trimester decidual dNKs suggests that these novel decidual ILCs might be present throughout pregnancy. Functional testing with permutation analysis revealed production of multiple factors by individual cells, with a preference for IFNγ and VEGF. Overall, our data suggests continuity of a unique decidual innate lymphocytes across pregnancy with a polyfunctional functional profile conducive for pregnancy.

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microRNA expression in innate lymphoid cells from human decidua

Project description:Innate lymphoid cells are a heterogeneous subset of lymphocytes deeply implicated in the innate immune responses to different pathogens, in lymphoid organogenesis and in the maintenance of tissue homeostasis. Group 3 innate lymphoid cells (ILC3) have been detected in human decidua, where they play a role in the early inflammatory phase favoring implantation and tissue remodeling as well as in the subsequent regulatory phase preventing fetal rejection and supporting neoangiogenesis. A balance between inflammation and immune tolerance is required to maintain pregnancy, thus maternal immune system must be controlled by finely tuned mechanisms. MicroRNAs (miRNAs) are small non-coding RNAs with important regulatory roles in immune cells, but their function in decidual ILC3 (dILC3) and decidual NK (dNK) cells is still undefined. Here, we examined the miRNome by microarray in these cells during the first trimester of pregnancy and compared with miRNA profiles of peripheral blood NK (pbNK) cells from pregnant women. We show that distinct miRNA profiles could clearly distinguish dILC3 from NK cells. Correlation analyses revealed that dNK and pbNK miRNome profiles are more similar to each other as compared to dILC3. Overall, our data identified specific miRNA signatures distinguishing dILC3, dNK and pbNK cells.

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Proteogenomic and V(D)J Analysis of Human Decidual T cells Highlights Unique Transcriptional Programming and Clonal Distribution [VDJ-seq]

Project description:Immunological tolerance towards the semi-allogeneic fetus is one of many maternal adaptations required for a successful pregnancy. T cells are major players of the adaptive immune system and balance tolerance and protection at the maternal-fetal interface, however, their repertoire and subset programming is still poorly understood. Utilizing emerging scRNA-seq technologies we simultaneously obtained transcript, limited protein, and receptor repertoire at the single-cell level, from decidual and matched maternal peripheral T cells. In agreement with previous work, we find that the decidua maintains a tissue-specific distribution of T cells compared to the periphery. We find that decidual T cells maintain a unique transcriptome programming, characterized by restraint of inflammatory pathways by overexpression of negative regulators. Furthermore, we show little clonal overlap between the decidua and periphery, suggesting minimal ongoing traffic between these scites. Overall, our data demonstrate the power of multi-omic analysis in revealing regulation of fetal-maternal immune co-existence.

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