title: Identity, regulation and in vivo function of gut NKp46+RORγt+ and NKp46+RORγt- lymphoid cells.
abstract: The gut is a major barrier against microbes and encloses various innate lymphoid cells (ILCs), including two subsets expressing the natural cytotoxicity receptor NKp46. A subset of NKp46(+) cells expresses retinoic acid receptor-related orphan receptor γt (RORγt) and produces IL-22, like lymphoid tissue inducer (LTi) cells. Other NKp46(+) cells lack RORγt and produce IFN-γ, like conventional Natural Killer (cNK) cells. The identity, the regulation and the in vivo functions of gut NKp46(+) ILCs largely remain to be unravelled. Using pan-genomic profiling, we showed here that small intestine (SI) NKp46(+)RORγt(-) ILCs correspond to SI NK cells. Conversely, we identified a transcriptional programme conserved in fetal LTi cells and adult SI NKp46(+)RORγt(+) and NKp46(-)RORγt(+) ILCs. We also demonstrated that the IL-1β/IL-1R1/MyD88 pathway, but not the commensal flora, drove IL-22 production by NKp46(+)RORγt(+) ILCs. Finally, oral Listeria monocytogenes infection induced IFN-γ production in SI NK and IL-22 production in NKp46(+)RORγt(+) ILCs, but only IFN-γ contributed to control bacteria dissemination. NKp46(+) ILC heterogeneity is thus associated with subset-specific transcriptional programmes and effector functions that govern their implication in gut innate immunity.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université de la Mediterannée, Campus du Luminy, Marseille, France.
authors.forename: Ana
authors.initials: A
authors.lastname: Reynders
authors.forename: Nadia
authors.initials: N
authors.lastname: Yessaad
authors.forename: Thien-Phong
authors.initials: TP
authors.lastname: Vu Manh
authors.forename: Marc
authors.initials: M
authors.lastname: Dalod
authors.forename: Aurore
authors.initials: A
authors.lastname: Fenis
authors.forename: Camille
authors.initials: C
authors.lastname: Aubry
authors.forename: Georgios
authors.initials: G
authors.lastname: Nikitas
authors.forename: Bertrand
authors.initials: B
authors.lastname: Escalière
authors.forename: Jean Christophe
authors.initials: JC
authors.lastname: Renauld
authors.forename: Olivier
authors.initials: O
authors.lastname: Dussurget
authors.forename: Pascale
authors.initials: P
authors.lastname: Cossart
authors.forename: Marc
authors.initials: M
authors.lastname: Lecuit
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.forename: Elena
authors.initials: E
authors.lastname: Tomasello
mesh_terms: D000818:Animals; D019070:Cell Lineage; D005260:Female; D005434:Flow Cytometry; D007113:Immunity, Innate; D007421:Intestine, Small / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008089:Listeria monocytogenes / Q000302:isolation & purification; D008088:Listeriosis / Q000378:metabolism / Q000382:microbiology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000235:genetics / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000502:physiology; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution; D000097768:Retinoic Acid Receptor gamma
chemical_list: D053594:Myeloid Differentiation Factor 88; D055627:Natural Cytotoxicity Triggering Receptor 1; D017472:Receptors, Interleukin-1; D018168:Receptors, Retinoic Acid; D000097768:Retinoic Acid Receptor gamma; C507780:Myd88 protein, mouse