title: Notch signaling in group 3 innate lymphoid cells modulates their plasticity.
abstract: The Notch signaling pathway is conserved throughout evolution, and it controls various processes, including cell fate determination, differentiation, and proliferation. Innate lymphoid cells (ILCs) are lymphoid cells lacking antigen receptors that fulfill effector and regulatory functions in innate immunity and tissue remodeling. Type 3 ILCs (ILC3s) reinforce the epithelial barrier and maintain homeostasis with intestinal microbiota. We demonstrated that the population of natural cytotoxicity receptor-positive (NCR(+)) ILC3s in mice is composed of two subsets that have distinct developmental requirements. A major subset depended on the activation of Notch2 in NCR(-) ILC3 precursors in the lamina propria of the small intestine to stimulate expression of the genes encoding the transcription factors T-bet, RORγt, and aryl hydrocarbon receptor (AhR). Notch signaling contributed to the transition of NCR(-) cells into NCR(+) cells, the more proinflammatory subset, in a cell-autonomous manner. In the absence of Notch signaling, this subset of NCR(-) ILC3s did not acquire the gene expression profile of NCR(+) ILC3s. A second subset of NCR(+) ILC3s did not depend on Notch for their development or for increased transcription factor abundance; however, their production of cytokines and cell surface abundance of NCRs were decreased in the absence of Notch signaling. Together, our data suggest that Notch is a regulator of the plasticity of ILC3s by controlling NCR(+) cell fate.
authors.affiliation: Lymphopoiesis Unit, Immunology Department, Institut Pasteur, 75015 Paris, France. Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, 75015 Paris, France. INSERM U1223, 75015 Paris, France.
authors.forename: Sylvestre
authors.initials: S
authors.lastname: Chea
authors.affiliation: Lymphopoiesis Unit, Immunology Department, Institut Pasteur, 75015 Paris, France. Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, 75015 Paris, France. INSERM U1223, 75015 Paris, France.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Perchet
authors.affiliation: Lymphopoiesis Unit, Immunology Department, Institut Pasteur, 75015 Paris, France. Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, 75015 Paris, France. INSERM U1223, 75015 Paris, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Petit
authors.affiliation: INSERM U1223, 75015 Paris, France. Innate Immunity Unit, Immunology Department, Institut Pasteur, 75015 Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Verrier
authors.affiliation: Lymphopoiesis Unit, Immunology Department, Institut Pasteur, 75015 Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Guy-Grand
authors.affiliation: Lymphopoiesis Unit, Immunology Department, Institut Pasteur, 75015 Paris, France. Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, 75015 Paris, France. INSERM U1223, 75015 Paris, France.
authors.forename: Elena-Gaia
authors.initials: EG
authors.lastname: Banchi
authors.affiliation: INSERM U1223, 75015 Paris, France. Innate Immunity Unit, Immunology Department, Institut Pasteur, 75015 Paris, France.
authors.forename: Christian A J
authors.initials: CA
authors.lastname: Vosshenrich
authors.affiliation: INSERM U1223, 75015 Paris, France. Innate Immunity Unit, Immunology Department, Institut Pasteur, 75015 Paris, France.
authors.forename: James P
authors.initials: JP
authors.lastname: Di Santo
authors.affiliation: Lymphopoiesis Unit, Immunology Department, Institut Pasteur, 75015 Paris, France. Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, 75015 Paris, France. INSERM U1223, 75015 Paris, France.
authors.forename: Ana
authors.initials: A
authors.lastname: Cumano
authors.affiliation: Lymphopoiesis Unit, Immunology Department, Institut Pasteur, 75015 Paris, France. Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, 75015 Paris, France. INSERM U1223, 75015 Paris, France. rachel.golub@pasteur.fr.
authors.forename: Rachel
authors.initials: R
authors.lastname: Golub
mesh_terms: D000818:Animals; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007378:Interleukins / Q000378:metabolism; D007422:Intestines; D008214:Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D016207:Cytokines; D007378:Interleukins; D051880:Receptors, Notch; D016212:Transforming Growth Factor beta