In Situ Maturation and Tissue Adaptation of Type 2 Innate Lymphoid Cell Progenitors

Zeis, Patrice; Mi, Lian; Fan, Xiying; Herman, Josip Stefan; Hernandez, Daniela; Gentek, Rebecca; Elias, Shlomo; Symowski, Cornelia; Knöpper, Konrad; Peltokangas, Nina; Friedrich, Chr.; Doucet‐Ladevèze, Rémi; Kabat, Agnieszka M.; Locksley, Richard M.; Voehringer, David; Bajénoff, Marc; Rudensky, Alexander Y.; Romagnani, Chiara; Grün, Dominic; Gasteiger, Georg

doi:10.1016/j.immuni.2020.09.002

Cited by 115 publications

(172 citation statements)

References 71 publications

(119 reference statements)

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“…We now demonstrate that mature (IL-5 producing) ILC2 display a very limited potential to differentiate into ILC1-like cells as evidenced using a fate-mapping approach. As described in recent reports 4,17 , lung ILC2 is a complex and heterogeneous population of cells with a broad spectrum of maturity. Although the identity of the immature ILC2 population giving rise to ILC1-like cells remains to be formally demonstrated, we identified an immature ILC2 subset, based on the expression of IL-18Ra, sharing phenotypic similarities with bone marrow ILC2P, which retains the ability to differentiate into ILC1-like cells.…”

Section: Discussionmentioning

confidence: 89%

“…1 and Supplementary Fig. 1) and others 16,17 reported the presence of a discrete subset of IL-18Ra + ILC2 at steady-state harboring a less activated phenotype compared to IL-18Ra -ILC2 and ILC2 precursor (ILC2P). To assess if immature ILC2, such as ILC2P from BM, have the potential to give rise to ILC1-like cells, we performed an in vitro differentiation assay in the presence of type 1 or type 2 activating cytokines.…”

Section: Pulmonary Ilc2 Give Rise To Ilc1-like Cells During Mtb Infecmentioning

confidence: 81%

“…Although the identity of the immature ILC2 population giving rise to ILC1-like cells remains to be formally demonstrated, we identified an immature ILC2 subset, based on the expression of IL-18Ra, sharing phenotypic similarities with bone marrow ILC2P, which retains the ability to differentiate into ILC1-like cells. These results raise the exciting possibility that local precursors formed by immature ILC2 may undergo an ILCpoiesis 16,17 controlled by the inflammatory context that may drive the generation of ILC subsets adapted to Mtb infection in the lungs, as suggest in human ILC biology 36,37 . In this regard, type 1 or type 2 environments triggered by cytokines drove the conversion of IL-18Ra + ILC2 toward mature ILC2 or ILC1-like cells, We report for the first time that newly generated ILC1-like cells critically depend on glycolytic metabolism that is independent of Arg1.…”

Section: Discussionmentioning

confidence: 94%

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Metabolic regulation of ILC2 differentiation into ILC1-like cells duringMycobacterium tuberculosisinfection

Corral

Charton

Krauss

et al. 2021

Preprint

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Tissue-resident innate lymphoid cells (ILCs) regulate tissue homeostasis and protect against pathogens at mucosal surfaces and are key players at the interface of innate and adaptive immunity. How ILCs adapt their phenotype and function to environmental cues in their tissue of residence remains to be fully understood. Here we show that Mycobacterium tuberculosis infection alters the biology of lung ILCs and, in particular, induces the emergence of a non-classical, protective, interferon-γ-producing ILC1-like population. Adoptive transfer, fate-mapping and in vitro differentiation experiments revealed that ILC1-like cells originate from immature ILC2 rather than from mature ILC2. This plasticity is controlled by type 1 cytokines and a glycolytic program involving the transcription factor HIF1α. Collectively, our data reveal how tissue-resident ILCs adapt to their inflammatory and metabolic environment to undergo phenotypic and functional changes toward a pathogen-adapted immune response.

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Section: Discussionmentioning

confidence: 89%

Section: Pulmonary Ilc2 Give Rise To Ilc1-like Cells During Mtb Infecmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 94%

See 1 more Smart Citation

Metabolic regulation of ILC2 differentiation into ILC1-like cells duringMycobacterium tuberculosisinfection

Corral

Charton

Krauss

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…Single cell RNAseq was performed on these cells and analysis based on expression similarity allowed the construction of predicted lineage path trajectories. This analysis suggests that the ILC2 present in repair can develop from ILC2 already present in the infected tissue indicative perhaps of the role of the environment in shaping ILC2 phenotype and function (36). Alternatively, this observation may show that pro-repair ILC2 are a more specialized and differentiated subset than other ILC2s.…”

Section: Heterogeneity In Ilc2 Repair Functionmentioning

confidence: 89%

“…Furin activates a wide range of pro-protein substrates in the secretory pathway of all cell types. Furin is increased in ILCs present during time points when healing occurs in N. brasiliensis infection (36). However, direct data to show ILC2 derived furin is reparative, is lacking.…”

Section: Furinmentioning

confidence: 99%

Maintenance of Barrier Tissue Integrity by Unconventional Lymphocytes

2021

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Mucosal surfaces, as a first barrier with the environment are especially susceptible to damage from both pathogens and physical trauma. Thus, these sites require tightly regulated repair programs to maintain barrier function in the face of such insults. Barrier sites are also enriched for unconventional lymphocytes, which lack rearranged antigen receptors or express only a limited range of such receptors, such as ILCs (Innate Lymphoid Cells), γδ T Cells and MAIT (Mucosal-Associated Invariant T Cells). Recent studies have uncovered critical roles for unconventional lymphocytes in regulating mucosal barrier function, and, in particular, have highlighted their important involvement in barrier repair. The production of growth factors such as amphiregulin by ILC2, and fibroblast growth factors by γδ T cells have been shown to promote tissue repair at multiple barrier sites. Additionally, MAIT cells have been shown to exhibit pro-repair phenotypes and demonstrate microbiota-dependent promotion of murine skin healing. In this review we will discuss how immune responses at mucosal sites are controlled by unconventional lymphocytes and the ways in which these cells promote tissue repair to maintain barrier integrity in the skin, gut and lungs.

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OMIP‐086: Full spectrum flow cytometry for high‐dimensional immunophenotyping of mouse innate lymphoid cells

Mincham

Snelgrove

2022

Cytometry Pt A

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This 25-parameter, 22-color full spectrum flow cytometry panel was designed and optimized for the comprehensive enumeration and functional characterization of innate lymphoid cell (ILC) subsets in mouse tissues. The panel presented here allows the discrimination of ILC progenitors (ILCP), ILC1, ILC2, NCR + ILC3, NCR À ILC3, CCR6 + lymphoid tissue-inducer (LTi)-like ILC3 and mature natural killer (NK) cell populations. Further characterization of ILC and NK cell functional profiles in response to stimulation is provided by the inclusion of subset-specific cytokine markers, and proliferation markers. Development and optimization of this panel was performed on freshly isolated cells from adult BALB/c lungs and small intestine lamina propria, and ex vivo stimulation with phorbol 12-myrisate 13-acetate, ionomycin, and pro-ILC activating cytokines.

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In Situ Maturation and Tissue Adaptation of Type 2 Innate Lymphoid Cell Progenitors

Cited by 115 publications

References 71 publications

Metabolic regulation of ILC2 differentiation into ILC1-like cells duringMycobacterium tuberculosisinfection

Metabolic regulation of ILC2 differentiation into ILC1-like cells duringMycobacterium tuberculosisinfection

Maintenance of Barrier Tissue Integrity by Unconventional Lymphocytes

OMIP‐086: Full spectrum flow cytometry for high‐dimensional immunophenotyping of mouse innate lymphoid cells

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