title: RORγt⁺ innate lymphoid cells acquire a proinflammatory program upon engagement of the activating receptor NKp44.
abstract: RORγt⁺ innate lymphoid cells (ILCs) are crucial players of innate immune responses and represent a major source of interleukin-22 (IL-22), which has an important role in mucosal homeostasis. The signals required by RORγt⁺ ILCs to express IL-22 and other cytokines have been elucidated only partially. Here we showed that RORγt⁺ ILCs can directly sense the environment by the engagement of the activating receptor NKp44. NKp44 triggering in RORγt⁺ ILCs selectively activated a coordinated proinflammatory program, including tumor necrosis factor (TNF), whereas cytokine stimulation preferentially induced IL-22 expression. However, combined engagement of NKp44 and cytokine receptors resulted in a strong synergistic effect. These data support the concept that NKp44⁺ RORγt⁺ ILCs can be activated without cytokines and are able to switch between IL-22 or TNF production, depending on the triggering stimulus.
authors.affiliation: Innate Immunity, Deutsches Rheuma-Forschungszentrum-Leibniz-Gemeinschaft, 10117 Berlin, Germany.
authors.forename: Timor
authors.initials: T
authors.lastname: Glatzer
authors.forename: Monica
authors.initials: M
authors.lastname: Killig
authors.forename: Johannes
authors.initials: J
authors.lastname: Meisig
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ommert
authors.forename: Merlin
authors.initials: M
authors.lastname: Luetke-Eversloh
authors.forename: Marina
authors.initials: M
authors.lastname: Babic
authors.forename: Daniela
authors.initials: D
authors.lastname: Paclik
authors.forename: Nils
authors.initials: N
authors.lastname: Blüthgen
authors.forename: Rainer
authors.initials: R
authors.lastname: Seidl
authors.forename: Claudia
authors.initials: C
authors.lastname: Seifarth
authors.forename: Jörn
authors.initials: J
authors.lastname: Gröne
authors.forename: Minoo
authors.initials: M
authors.lastname: Lenarz
authors.forename: Katharina
authors.initials: K
authors.lastname: Stölzel
authors.forename: Dominik
authors.initials: D
authors.lastname: Fugmann
authors.forename: Angel
authors.initials: A
authors.lastname: Porgador
authors.forename: Anja
authors.initials: A
authors.lastname: Hauser
authors.forename: Alexander
authors.initials: A
authors.lastname: Karlas
authors.forename: Chiara
authors.initials: C
authors.lastname: Romagnani
mesh_terms: D002478:Cells, Cultured; D060833:Cellular Microenvironment; D006706:Homeostasis; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology*; D009092:Mucous Membrane / Q000276:immunology; D055629:Natural Cytotoxicity Triggering Receptor 2 / Q000276:immunology / Q000378:metabolism*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D020239:Receptor Cross-Talk; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D018836:Inflammation Mediators; D007378:Interleukins; D055629:Natural Cytotoxicity Triggering Receptor 2; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D014409:Tumor Necrosis Factor-alpha; D000097043:Interleukin-22