RNA sequencing of lung innate lymphoid cell (ILC) populations
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE125816 | GEO | 2020/03/02
REPOSITORIES: GEO
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Project description:Activated type 2 innate lymphoid cells (ILC2s) accumulate and promote inflammatory resolution and tissue repair in host defense against acute respiratory viral infections. However, whether an ILC2 subset that specializes in wound healing exists, and the mechanisms by which ILC2 cells contribute to tissue repair remain elusive. Using single-cell RNA-sequencing (scRNA-seq), we identified a transcriptionally distinct ILC2 subset that showed enrichment for wound healing signature genes and the transcription factor BATF. Notably, BATF promoted the proliferation and function of ILC2s and restricted their plasticity during infection with influenza virus. In the absence of BATF, ILC2s lost their immune protective properties and obtained pathogenic ILC3-like function, which led to persist neutrophil infiltration, tissue damage and lethality. Mechanistically, BATF directly bound the cis-regulatory elements of wound healing genes, maintained their chromatin accessibility and promoted their expression. Lastly, BATF played an important role in an IL-33-ST2 feed-forward loop that supports ILC2 cell identity and function. Collectively, our findings shed light on a BATF-dependent ILC2 program thereby providing a potential therapeutic target for terminating detrimental inflammation during acute viral infection.
2022-01-14 | GSE149857 | GEO
Project description:Activated type 2 innate lymphoid cells (ILC2s) accumulate and promote inflammatory resolution and tissue repair in host defense against acute respiratory viral infections. However, whether an ILC2 subset that specializes in wound healing exists, and the mechanisms by which ILC2 cells contribute to tissue repair remain elusive. Using single-cell RNA-sequencing (scRNA-seq), we identified a transcriptionally distinct ILC2 subset that showed enrichment for wound healing signature genes and the transcription factor BATF. Notably, BATF promoted the proliferation and function of ILC2s and restricted their plasticity during infection with influenza virus. In the absence of BATF, ILC2s lost their immune protective properties and obtained pathogenic ILC3-like function, which led to persist neutrophil infiltration, tissue damage and lethality. Mechanistically, BATF directly bound the cis-regulatory elements of wound healing genes, maintained their chromatin accessibility and promoted their expression. Lastly, BATF played an important role in an IL-33-ST2 feed-forward loop that supports ILC2 cell identity and function. Collectively, our findings shed light on a BATF-dependent ILC2 program thereby providing a potential therapeutic target for terminating detrimental inflammation during acute viral infection.
2022-01-14 | GSE149854 | GEO
Project description:Activated type 2 innate lymphoid cells (ILC2s) accumulate and promote inflammatory resolution and tissue repair in host defense against acute respiratory viral infections. However, whether an ILC2 subset that specializes in wound healing exists, and the mechanisms by which ILC2 cells contribute to tissue repair remain elusive. Using single-cell RNA-sequencing (scRNA-seq), we identified a transcriptionally distinct ILC2 subset that showed enrichment for wound healing signature genes and the transcription factor BATF. Notably, BATF promoted the proliferation and function of ILC2s and restricted their plasticity during infection with influenza virus. In the absence of BATF, ILC2s lost their immune protective properties and obtained pathogenic ILC3-like function, which led to persist neutrophil infiltration, tissue damage and lethality. Mechanistically, BATF directly bound the cis-regulatory elements of wound healing genes, maintained their chromatin accessibility and promoted their expression. Lastly, BATF played an important role in an IL-33-ST2 feed-forward loop that supports ILC2 cell identity and function. Collectively, our findings shed light on a BATF-dependent ILC2 program thereby providing a potential therapeutic target for terminating detrimental inflammation during acute viral infection.
2022-01-14 | GSE149849 | GEO
Project description:Activated type 2 innate lymphoid cells (ILC2s) accumulate and promote inflammatory resolution and tissue repair in host defense against acute respiratory viral infections. However, whether an ILC2 subset that specializes in wound healing exists, and the mechanisms by which ILC2 cells contribute to tissue repair remain elusive. Using single-cell RNA-sequencing (scRNA-seq), we identified a transcriptionally distinct ILC2 subset that showed enrichment for wound healing signature genes and the transcription factor BATF. Notably, BATF promoted the proliferation and function of ILC2s and restricted their plasticity during infection with influenza virus. In the absence of BATF, ILC2s lost their immune protective properties and obtained pathogenic ILC3-like function, which led to persist neutrophil infiltration, tissue damage and lethality. Mechanistically, BATF directly bound the cis-regulatory elements of wound healing genes, maintained their chromatin accessibility and promoted their expression. Lastly, BATF played an important role in an IL-33-ST2 feed-forward loop that supports ILC2 cell identity and function. Collectively, our findings shed light on a BATF-dependent ILC2 program thereby providing a potential therapeutic target for terminating detrimental inflammation during acute viral infection.
2022-01-14 | GSE149847 | GEO
Project description:Activated type 2 innate lymphoid cells (ILC2s) accumulate and promote inflammatory resolution and tissue repair in host defense against acute respiratory viral infections. However, the heterogeneity of ILC2s in the lung and the mechanisms by which ILC2 cells contribute to tissue repair remain elusive. Using single-cell RNA-sequencing (scRNA-seq), we identified a transcriptionally distinct ILC2 subset that showed enrichment for wound healing signature genes and the transcription factor BATF. Notably, BATF promoted the proliferation and function of ILC2s and restricted their plasticity during infection with influenza virus. In the absence of BATF, ILC2s lost their immune protective properties and obtained pathogenic ILC3-like function, which led to persist neutrophil infiltration, tissue damage and lethality. Mechanistically, BATF directly bound the cis-regulatory elements of wound healing genes, maintained their chromatin accessibility and promoted their expression. Lastly, BATF played an important role in an IL-33-ST2 feed-forward loop that supports ILC2 cell identity and function. Collectively, our findings shed light on a BATF-dependent ILC2 program, thereby providing a potential therapeutic target for terminating detrimental inflammation during acute viral infection.
2022-01-14 | GSE188275 | GEO
Project description:Recently, circulating multi- and uni-potent human ILC precursors (ILCP) have been found in a lymphocyte population that expresses CD117 and CD127 but lacks CRTH2 and NKp44. However, these ILCPs have not been extensively characterized. We performed an unbiased Hierarchical Stochastic Neighbor Embedding (HSNE) analysis of the phenotype of peripheral blood CD117+ ILCPs which revealed the presence of three major subsets: the first expressed NKp46, the second expressed both NKp46 and CD56, while the third expressed KLRG1. Analysis of their differentiation potential on bulk and clonal levels, cytokine production and the transcriptome revealed that the NKp46+ ILCPs contain high frequencies of ILC3 precursors whereas a minority can differentiate into ILC1/NK-like cells. In contrast, KLRG1+ ILCPs are biased to the ILC2 lineage, but are highly plastic and epigenetically primed to differentiate into other ILC subsets depending on the activation signals they receive.
2019-06-05 | GSE124054 | GEO
Project description: Not available
| S-EPMC4761490 | biostudies-literature
Project description:Group 2 innate lymphoid cells (ILC-2s) regulate immune responses to pathogens, allergens, tissue remodeling and metabolic homeostasis in response to cytokines. Positive regulation of ILC-2s through ICOS has been recently elucidated but co-receptor mediated negative regulatory axis is yet to be defined. We demonstrate that PD-1 is an important negative regulator of KLRG1+ILC-2 function in both mice and humans. Increase in KLRG1+ ILC-2 cells numbers were attributed to an intrinsic defect in PD-1 signaling, which resulted in enhanced STAT5 activation. During Nippostrongylus brasiliensis infection, a significant expansion of KLRG1+ ILC-2 subsets occurred in pdcd1-/- mice and on adoptive transfer, pdcd1-/- KLRG1+ ILC-2s significantly reduced worm burden. Furthermore, blocking antibody to PD-1 increased KLRG1+ ILC-2 cell number and reduced disease burden. Therefore PD-1 is an important negative regulator and is vital for maintaining the number and hence function of KLRG1+ ILC-2s.
2017-05-04 | GSE94609 | GEO
Project description:Type-2 innate lymphoid cells (ILC2s) promote anti-helminth responses and contribute to allergies. Though Bcl11b has been previously considered a T-lineage identity transcription factor (TF) that restrains the innate-cell genetic programs, we report here that Bcl11b is highly expressed in mature ILC2s and acts upstream of the key ILC2 TFs Gfi1, Gata-3, and of IL-33 receptor IL1rl1 (T1ST2). Additionally, Bcl11b-/- ILC2s de-repressed Rorγt, Ahr and IL-23 receptor, normally expressed in type-3 ILCs (ILC3s). Consequently, Bcl11b-/- ILC2s lost ILC2 functions and gained ILC3 functions, expanding in response to the protease allergen papain, however producing IL-17 and IL-22, and not IL-5 and IL-13, causing lung neutrophilia rather than eosinophilia, and diminished mucus production. Our results broaden Bcl11b's role from a T-cell only TF, and establishes that Bcl11b sustains mature ILC2 genetic and functional programs and lineage fidelity through positive regulation of essential ILC2 TFs and negative regulation of pivotal ILC3 TFs. RNA-seq analysis on sorted ILC2s from the mLNs of Bcl11bF/F Cre-ERT2 and wildtype mice at steady state following tamoxifen mediated deletion of Bcl11b
2015-07-28 | E-GEOD-67437 | biostudies-arrayexpress
Project description:Here we identify the c-kit+ CILP population which generates all ILC subsets including NK cells, and the CD25- ILC2-restricted Sca-1+ CILP. We mapped the transcriptional changes that occur in ILC progenitor commitment identifying new regulatory factors and provide a map for early ILC differentiation. Finally, we mapped the subsequent transcriptional changes that occur in c-kit+ CILP in absence of Id2 and Tcf7, key regulators downstream of Nfil3.
2016-10-04 | GSE75851 | GEO