Systemic human ILC precursors provide a substrate for tissue ILC differentiation
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- dc.contributor.author Lim, Ai Ingca
- dc.contributor.author Stadhouders, Ralphca
- dc.contributor.author Graf, T. (Thomas)ca
- dc.contributor.author Di Santo, James P.ca
- dc.date.accessioned 2018-05-18T08:29:26Z
- dc.date.available 2018-05-18T08:29:26Z
- dc.date.issued 2017
- dc.description.abstract Innate lymphoid cells (ILCs) represent innate versions of T helper and cytotoxic T cells that differentiate from committed ILC precursors (ILCPs). How ILCPs give rise to mature tissue-resident ILCs remains unclear. Here, we identify circulating and tissue ILCPs in humans that fail to express the transcription factors and cytokine outputs of mature ILCs but have these signature loci in an epigenetically poised configuration. Human ILCPs robustly generate all ILC subsets in vitro and in vivo. While human ILCPs express low levels of retinoic acid receptor (RAR)-related orphan receptor C (RORC) transcripts, these cells are found in RORC-deficient patients and retain potential for EOMES+ natural killer (NK) cells, interferon gamma-positive (IFN-γ+) ILC1s, interleukin (IL)-13+ ILC2s, and for IL-22+, but not for IL-17A+ ILC3s. Our results support a model of tissue ILC differentiation ("ILC-poiesis"), whereby diverse ILC subsets are generated in situ from systemically distributed ILCPs in response to local environmental signals.
- dc.description.sponsorship A.I.L. is a scholar in Pasteur-Paris University (PPU) International PhD program and supported by FP7 under grant agreement 317057 (HOMIN) and the Fondation ARC. R.S. was supported by EMBO (ALTF 1201-2014) and Marie Curie (H2020-MSCA-IF-2014). Other support included grants from the Institut Pasteur, Inserm, Laboratoire d'Excellence REVIVE (ANR-10-LBX-73), and FP7 under grant agreement HEALTH-F3-2012-305578 (PathCO) and 317057 (HOMIN). J.P.D. is a founder of AXENIS and a member of its advisory board.
- dc.format.mimetype application/pdf
- dc.identifier.citation Lim AI, Li Y, Lopez-Lastra S, Stadhouders R, Paul F, Casrouge A et al. Systemic Human ILC Precursors Provide a Substrate for Tissue ILC Differentiation. Cell 2017 Mar; 168(6): 1086-1100.e10. DOI: 10.1016/j.cell.2017.02.021
- dc.identifier.doi http://dx.doi.org/10.1016/j.cell.2017.02.021
- dc.identifier.issn 0092-8674
- dc.identifier.uri http://hdl.handle.net/10230/34685
- dc.language.iso eng
- dc.publisher Elsevierca
- dc.relation.ispartof Cell 2017 Mar; 168(6): 1086-1100.e10
- dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/317057
- dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/305578
- dc.rights © Elsevier This is the published version of an article http://dx.doi.org/10.1016/j.cell.2017.02.021 that appeared in the journal Cell. It is published in an Open Archive under an Elsevier user license. Details of this licence are available here: https://www.elsevier.com/about/our-business/policies/open-access-licenses/elsevier-user-license
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.subject.keyword Cell fate
- dc.subject.keyword Cytokines
- dc.subject.keyword Humanized mice
- dc.subject.keyword Innate lymphoid cells
- dc.subject.keyword Lymphopoiesis
- dc.subject.keyword Signaling
- dc.subject.keyword Single cell cloning
- dc.subject.keyword Transcription factors
- dc.title Systemic human ILC precursors provide a substrate for tissue ILC differentiationca
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion