ILC2 lymphoid development in inflammatory conditions

 

Responsable du Stage : Pr Rachel Golub

Tél : 01 45 68 87 66      E-mail: rgolub@pasteur.fr

Institut Pasteur

Résumé du Projet de Stage 

Group 2 innate lymphoid cells (ILC2s) are tissue resident lymphocytes with effector functions within the mucosa. ILC2s are key actors in type 2 immune responses in the context of allergic inflammation, infection and numerous other diseases related to fibrosis. ILC2s develop in the bone marrow (BM) from common lymphoid progenitor cells, but little is known about how inflammation could enhance ILC2 development and migration toward inflamed tissues. Moreover, the stage of development at which ILC2s leave the bone marrow for peripheral tissue colonization is unclear. We propose a study comparing ILC2 development in steady-state versus TH2 induced inflammatory conditions. Moreover, mice that were maintained under germ free conditions will also be compared for ILC2 development and in order to understand whether regulation of ILC2 production in the bone marrow could be directly or indirectly regulated by the microbiota and their derived-metabolites. IL-33 was identified as a hallmark of peripheral ILC2-activating cytokine, and could promote ILC2s egress from the bone marrow. BM‐derived ILC2s are recruited to fibrotic lung through this IL‐33/ST2 pathway, and contribute to fibroblast activation to promote lung fibrosis. It is therefore important to understand how BM derived ILC2s are polarized in the BM and the molecular mechanisms enhancing their migration to the lung.

Dernières Publications en lien avec le projet :

  1. Cumano A, Berthault C, Ramond C, Petit M, Golub R, Bandeira A, Pereira P. New Molecular Insights into Immune Cell Development. Annu Rev Immunol. 2019 Apr 26;37:497-519.
  2. Xu W, Cherrier D, Chea S, Vosshenrich C, Serafini N, Petit M, Liu P, Golub R, Di Santo J (2019) A novel Id2RFP reporter mouse strain redefines ILC precursor potentials. Immunity 50:1054.
  3. Maintenance of Type 2 Response by CXCR6-Deficient ILC2 in Papain-Induced Lung Inflammation. Meunier S, Chea S, Garrido D, Perchet T, Petit M, Cumano A & Golub R (2019) J. Mol. Sci. 20(21), 5493.
  4. Beuraud C, Lombardi V, Luce S, Horiot S, Naline E, Neukirch C, Airouche S, Perchet T, Golub R, P Devillier P, Chollet-Martin S, Baron-Bodo V, Nony E, Aubier M, Mascarell L, Moingeon P (2019) CCR10+ ILC2s with ILC1-like properties exhibit a protective function in severe allergic asthma. Allergy 74(5):933-943.
  5. Berthault C, Ramond C, Burlen-Defranoux O, Soubigou G, Chea S, Golub R, Pereira P, Vieira P, Cumano A. (2017) Asynchronous lineage priming determines commitment to T cell and B cell lineages in fetal liver. Nat Immunol. 18(10):1139-1149.
  6. Ishizuka IE*, Chea S*, Gudjonson H, Constantinides MG, Dinner AR, Bendelac A & Golub R (2016) Single cell analysis defines the divergence between the innate lymphoid cell lineage and lymphoid tissue–inducer cell lineage. Nat Immunol. 17(3):269-76.

Ce projet s’inscrit-il dans la perspective d’une thèse :
oui X

ED d’appartenance : BioSPC

FicheaccueilM2-BMC-2021-2022-R Golub

Intitulé de l’Unité : Lymphocytes et Immunité

Nom du Responsable de l’Unité : Pr Ana Cumano
Nom du Responsable de l’Équipe : Pr Rachel Golub

Institut Pasteur, 25 Rue du docteur Roux, 75015 Paris