دورية أكاديمية
Notch, RORC and IL-23 signals cooperate to promote multi-lineage human innate lymphoid cell differentiation
| العنوان: | Notch, RORC and IL-23 signals cooperate to promote multi-lineage human innate lymphoid cell differentiation |
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| المؤلفون: | Croft, Carys, A, Thaller, Anna, Marie, Solenne, Doisne, Jean-Marc, Surace, Laura, Yang, Rui, Puel, Anne, Bustamante, Jacinta, Casanova, Jean-Laurent, Di Santo, James, P. |
| المساهمون: | Immunité Innée - Innate Immunity, Institut Pasteur Paris (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Rockefeller University New York, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Necker - Enfants Malades AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Howard Hughes Medical Institute (HHMI), Funding was provided by Institut Pasteur, the Institut National de la Santé et de la Recherche Médicale (Inserm), the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (695467 – ILC_REACTIVITY), the National Institute of Allergy and Infectious Diseases, NIH (R01AI095983) and the French National Research Agency (ANR) GENMSMD (ANR-16-CE17-0005-01) to J.P.D. C.A.C. is enrolled in the Pasteur-Paris University (PPU) International PhD Program that receives funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement #665807, from the Labex Revive (10-LABX-0073), Institut Pasteur and the Fondation ARC. A.T. received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement #765104., We are indebted to the patients and their families for their essential collaboration. We thank members on Innate Immunity Unit for the helpful discussions, and the Center for Translational Science (CRT)- Cytometry and Biomarkers Unit of Technology and Service (CB UTechS) at Institut Pasteur for their technical support., ANR-16-CE17-0005,GENMSMD,Dissection génétique de la Susceptibilité Mendélienne aux infections mycobactériennes chez l'homme(2016), ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), European Project: 695467,H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) ,ILC_REACTIVITY(2016) |
| المصدر: | ISSN: 2041-1723. |
| بيانات النشر: | HAL CCSD Nature Publishing Group |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | MESH: Cell Differentiation, MESH: Humans, MESH: Immunity, Innate, MESH: Interleukin-23, MESH: Killer Cells, Natural, MESH: Lymphocytes, MESH: Lymphoid Progenitor Cells, MESH: Nuclear Receptor Subfamily 1, Group F, Member 3, MESH: Receptors, Notch, [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; Abstract Innate lymphoid cells (ILCs) include cytotoxic natural killer cells and distinct groups of cytokine-producing innate helper cells which participate in immune defense and promote tissue homeostasis. Circulating human ILC precursors (ILCP) able to generate all canonical ILC subsets via multi-potent or uni-potent intermediates according to our previous work. Here we show potential cooperative roles for the Notch and IL-23 signaling pathways for human ILC differentiation from blood ILCP using single cell cloning analyses and validate these findings in patient samples with rare genetic deficiencies in IL12RB1 and RORC . Mechanistically, Notch signaling promotes upregulation of the transcription factor RORC , enabling acquisition of Group 1 (IFN-γ) and Group 3 (IL-17A, IL-22) effector functions in multi-potent and uni-potent ILCP. Interfering with RORC or signaling through its target IL-23R compromises ILC3 effector functions but also generally suppresses ILC production from multi-potent ILCP. Our results identify a Notch->RORC- > IL-23R pathway which operates during human ILC differentiation. These observations may help guide protocols to expand functional ILC subsets in vitro with an aim towards novel ILC therapies for human disease. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/35896601; info:eu-repo/grantAgreement//695467/EU/Biological Determinants of ILC Reactivity for Immune Responses in Health and Disease/ILC_REACTIVITY; pasteur-04130561; https://pasteur.hal.science/pasteur-04130561Test; https://pasteur.hal.science/pasteur-04130561/documentTest; https://pasteur.hal.science/pasteur-04130561/file/s41467-022-32089-3.pdfTest; PUBMED: 35896601; PUBMEDCENTRAL: PMC9329340 |
| DOI: | 10.1038/s41467-022-32089-3 |
| الإتاحة: | https://doi.org/10.1038/s41467-022-32089-3Test https://pasteur.hal.science/pasteur-04130561Test https://pasteur.hal.science/pasteur-04130561/documentTest https://pasteur.hal.science/pasteur-04130561/file/s41467-022-32089-3.pdfTest |
| حقوق: | http://creativecommons.org/licenses/byTest/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.876A272F |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-022-32089-3 |
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