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Hobit confers tissue dependent programs to type 1 innate lymphoid cells

ABSTRACT: Innate responses against viral infection and other intracellular pathogens rely on immune cells that are capable of lysing infected cells and producing interferon-gamma (IFNγ). These cells encompass two major cell lineages: natural killer (NK) cells and type 1 innate lymphoid cells (ILC1s). While NK cells have been extensively characterized, identification of ILC1s and their distinction from NK cells is less clear. The transcription factor Hobit encoded by Zfp683 has been put forth as a prototypic feature of ILC1s. By analyzing Zfp683 reporter, fate-map and deficient mice, we demonstrate that the impact of Hobit on ILC1 identity, transcriptional and functional programs is tissue- and context-dependent. Thus, ILC1s functionally adapt to local stimuli and tailor their responses to the tissue niche.

ORGANISM(S): Mus musculus

PROVIDER: GSE185346 | GEO | 2021/12/06

REPOSITORIES: GEO

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Effector differentiation downstream of lineage commitment in ILC1 is driven by Hobit across tissues.

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SMAD4 impedes conversion of NK cells into ILC1-like cells by curtailing non-canonical TGFb signaling (mouse data sets)

Project description:Among the features that distinguish type 1 innate lymphoid cells (ILC1s) from NK cells is a gene signature indicative of TGFb-family cytokine imprinting. To assess the impact of TGFb family cytokines on ILC1 differentation, we examined SMAD4- a transcription factor that facilitates the signaling pathway common to all TGFb family cytokines-was specifically ablated in ILCs and NK cells. While SMAD4 deficiency did not affect ILC1 differentation, NK cells paradoxically aquired an ILC1-like gene signature and were incapable of controlling tumor metastasis and viral infection. We used microarray to define the transcriptional differences between splenic NK cells from WT and SMAD4F/F x Ncr1-Cre mice.

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Project description:Among the features that distinguish type 1 innate lymphoid cells (ILC1s) from NK cells is a gene signature indicative of TGFb-family cytokine imprinting. To assess the impact of TGFb family cytokines on ILC1 differentation, we examined SMAD4- a transcription factor that facilitates the signaling pathway common to all TGFb family cytokines-was specifically ablated in ILCs and NK cells. While SMAD4 deficiency did not affect ILC1 differentation, NK cells paradoxically aquired an ILC1-like gene signature and were incapable of controlling tumor metastasis and viral infection. We used microarray to compare the transcriptional differences between human blood NK cells. NK cells from a patient with a deleterious SMAD4 mutation or control NK cells were cultured overnight with either IL-2 alone or TGFb1 and IL-2.

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2021-05-04 | GSE158547 | GEO

scRNASeq of human innate lymphoid cells from different compartments

Project description:Group 1 innate lymphoid cells (ILCs) comprise a heterogeneous family of cytotoxic natural killer (NK) cells and ILC1s. We identifiy a population of Ã¢Â€Âœliver-typeÃ¢Â€Â ILC1s with transcriptional, phenotypic, and functional features distinct from those of conventional and liver-resident NK cells as well as from other previously described human ILC1 subsets. LT-ILC1s were CD49a+CD94+CD200R1+, expressed the transcription factor T-BET, do not express the activating receptor NKp80, or the transcription factor EOMES. Similar to NK cells, liver-type ILC1s produce IFN-ÃŽÂ³, TNF-ÃŽÂ±, and GM-CSF; however, liver-type ILC1s also produce IL-2 and lack perforin and granzyme B. Liver- type ILC1s are expanded in cirrhotic liver tissues, and they can be produced from blood-derived ILC precursors in vitro in the presence of TGF-ÃŽÂ²1 and liver sinusoidal endothelial cells. Cells with similar signature and function can also be found in tonsil and intestinal tissues. Collectively, our study identifies and classifies a population of human cross-tissue ILC1s.

| EGAS00001006847 | EGA

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