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

ABSTRACT: Innate lymphoid cells (ILCs) are generated early during ontogeny and persist predominantly as tissue-resident cells. Here, we examined how ILCs are maintained and renewed within tissues. We generated a single cell atlas of lung ILC2s and found that Il18r1⁺ ILCs comprise circulating and tissue-resident ILC progenitors (ILCP) and effector-cells with heterogeneous expression of the transcription factors Tcf7 and Zbtb16, and CD103. Our analyses revealed a continuous differentiation trajectory from Il18r1⁺ ST2^- ILCPs to Il18r^- ST2⁺ ILC2s, which was experimentally validated. Upon helminth infection, recruited and BM-derived cells generated the entire spectrum of ILC2s in parabiotic and shield chimeric mice, consistent with their potential role in the renewal of tissue ILC2s. Our findings identify local ILCPs and reveal ILCP in situ differentiation and tissue adaptation as a mechanism of ILC maintenance and phenotypic diversification. Local niches, rather than progenitor origin, or the developmental window during ontogeny, may dominantly imprint ILC phenotypes in adult tissues.

SUBMITTER: Zeis P

PROVIDER: S-EPMC7611573 | biostudies-literature |

REPOSITORIES: biostudies-literature

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

Project description:We analyzed the full spectrum of lung ILC2s at single-cell transcriptome resolution and identified an immature population of Il18r1+ tissue-associated ILCs, that express Tcf7 and Zbtb16, transcription factors known to act in ILC progenitors, and low levels of Gata3, ST2 and ILC2 effector molecules. We revealed a continuous differentiation trajectory and validated the potential of immature Il18r1+ cells to differentiate into Gata3hi ILC2s. We found that immature ILCs were recruited into the adult lung of parabiotic and shield chimeric mice during helminth infection. Intriguingly, recruited cells generated the entire spectrum of ILC2s in the lung, consistent with their potential role in the renewal of tissue ILC2s. Our work identifies local ILC progenitors and highlights their tissue adaptation and in situ differentiation as a mechanism of ILC maintenance and phenotypic diversification

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

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

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Human Innate Lymphoid Cell Subsets Possess Tissue-Type Based Heterogeneity in Phenotype and Frequency.

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Project description:Natural Killer (NK) cells at different developmental stages (common lymphoid progenitor (CLP), innate lymphoid cell progenitors (ILCP), and refined NK progenitor (NKP)) were collected from Vav1+iCre FOXO1,3flox/flox mice (C57BL/6 background). Total RNA was harvested and sequenced with a strand-specific paired-end RNA-seq protocol.

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Reduction of circulating innate lymphoid cell progenitors results in impaired cytokine production by innate lymphoid cells in patients with lupus nephritis.

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Single-cell analysis defines the divergence between the innate lymphoid cell lineage and lymphoid tissue-inducer cell lineage.

Project description:The precise lineage relationship between innate lymphoid cells (ILCs) and lymphoid tissue-inducer (LTi) cells is poorly understood. Using single-cell multiplex transcriptional analysis of 100 lymphoid genes and single-cell cultures of fetal liver precursor cells, we identified the common proximal precursor to these lineages and found that its bifurcation was marked by differential induction of the transcription factors PLZF and TCF1. Acquisition of individual effector programs specific to the ILC subsets ILC1, ILC2 and ILC3 was initiated later, at the common ILC precursor stage, by transient expression of mixed ILC1, ILC2 and ILC3 transcriptional patterns, whereas, in contrast, the development of LTi cells did not go through multilineage priming. Our findings provide insight into the divergent mechanisms of the differentiation of the ILC lineage and LTi cell lineage and establish a high-resolution 'blueprint' of their development.

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