Equipe d’Accueil :
Intitulé de l’Unité : Macrophages et cellules endothéliales
Nom du Responsable de l’Unité : Dr Elisa Gomez Perdiguero
Nom du Responsable de l’Équipe : Pr Rachel Golub
Adresse : Institut Pasteur, 25 Rue du docteur Roux, 75015 Paris
Responsable de l’encadrement : Marie Cherrier
Tél : 01 45 68 87 66 Fax : 01 45 68 84 21 E-mail: cherrier@pasteur.fr, rachel.golub@pasteur.fr
Résumé du projet
Innate lymphoid cells are immune effectors residing in non-lymphoid tissues where they participate in vertebrate host responses against viruses, fungi, parasites and extracellular bacteria. Tissue resident ILCs are also involved in regeneration and homeostasis through their ability to interact closely with epithelial and mesenchymal cells. Type 2 ILCs have been described as the innate counterpart of type 2 helper T cells based on the expression of the transcription factor GATA-3 and the production of type 2 cytokines such as IL-5 and IL-13. Type 2 ILCs respond to alarmins produced by epithelial cells and mesenchymal cells upon infection, challenge with allergens and tissue damage. ILCs are enriched at barrier tissues and ILC2s are commonly found in the lung and small intestine at steady state. It has been demonstrated that the tissue in which they reside endows ILCs with unique anticipatory functions regardless of their origin and subtype. However, which tissue specific microenvironmental cues are involved, how such signals are conveyed and which ILC developmental stage(s) are permissive to such “imprinting” remains unclear. Notch signaling is one of the major signaling pathways involved in cell fate decision across multiple cell lineages including hematopoietic and lymphoid cells. Notch receptors expressed by hematopoietic and lymphoid progenitors interact with multiple ligands mostly expressed by non-hematopoietic cells including mesenchymal and epithelial cells. Our lab already demonstrated that Notch signaling plays an essential role in the maturation and plasticity of gut resident NKp46+ ILC3s. We are now accumulating evidence that the function of type 2 ILCs is severly impaired in the absence of Notch signaling in vivo. Our aim is to further determine how Notch signaling shapes the function of tissue resident type 2 innate lymphoid cells in the lung and small intestine. A combination of in vivo and in vitro approaches will be used as well as a throughout molecular characterization of tissue resident ILCs in mice competent or deficient for Notch signaling in lymphoid lineage to precisely assess whether and how this signaling pathway instructs the final maturation stages of tissue resident ILC2s.
Dernières Publications en lien avec le projet :
1- Cherrier M, Teck Hui T, Corrêa Renan O, Picard M, Couesnon A, Lebreton C, Carbone F, Masson C, Schnupf P, Cerf-Bensussan N, Gaboriau-Routhiau V. Hematopoietic MyD88 orchestrates the control of gut colonization by segmented filamentous bacteria. Mucosal Immunol. 2025 Mar 14:S1933-0219(25)00028-5. doi: 10.1016/j.mucimm.2025.03.002
2- Bresler P, Tejerina E, Jacob JM, Legrand A, Quellec V, Ezine S, Peduto L, Cherrier M. T cells regulate lymph node-resident ILC populations in a tissue and subset-specific way. iScience. 2021 Feb 7;24(3):102158. doi:10.1016/j.isci.2021.102158. PMID: 33665576; PMCID: PMC7907429.
3- Cherrier M, Ramachandran G, Golub R. The interplay between innate lymphoid cells and T cells. Mucosal Immunol. 2020 Sep;13(5):732-742. doi:10.1038/s41385-020-0320-8. Epub 2020 Jul 10. PMID: 32651476.
4- Perchet T, Petit M, Banchi EG, Meunier S, Cumano A, Golub R (2018) The Notch Signaling Pathway Is Balancing Type 1 Innate Lymphoid Cell Immune Functions. Front Immunol. 9:1252.
5- Chea S, Perchet T, Petit M, Verrier T, Guy-Grand D, Banchi EG, Vosshenrich CAJ, Di Santo JP, Cumano A. & Golub R (2016) Notch signaling in group 3 ILC modulates their plasticity. Sci Signal. 9(426):ra45.
Ce projet s’inscrit dans la perspective d’une thèse
Type de financement prévu : Concours ED
Ecole Doctorale de rattachement : BioSPC