title: Regulated expression of nuclear receptor RORγt confers distinct functional fates to NK cell receptor-expressing RORγt(+) innate lymphocytes.
abstract: Whether the recently identified innate lymphocyte population coexpressing natural killer cell receptors (NKRs) and the nuclear receptor RORγt is part of the NK or lymphoid tissue inducer (LTi) cell lineage remains unclear. By using adoptive transfer of genetically tagged LTi-like cells, we demonstrate that NKR⁻RORγt(+) innate lymphocytes but not NK cells were direct progenitors to NKR(+)RORγt(+) cells in vivo. Genetic lineage tracing revealed that the differentiation of LTi-like cells was characterized by the stable upregulation of NKRs and a progressive loss of RORγt expression. Whereas interleukin-7 (IL-7) and intestinal microbiota stabilized RORγt expression within such NKR-LTi cells, IL-12 and IL-15 accelerated RORγt loss. RORγt(+) NKR-LTi cells produced IL-22, whereas RORγt⁻ NKR-LTi cells released IFN-γ and were potent inducers of colitis. Thus, the RORγt gradient in NKR-LTi cells serves as a tunable rheostat for their functional program. Our data also define a previously unappreciated role of RORγt⁻ NKR-LTi cells for the onset or maintenance of inflammatory bowel diseases.
authors.affiliation: IMMH, Institute of Medical Microbiology & Hygiene, University of Freiburg, 79104 Freiburg, Germany. cedric.vonarbourg@uniklinik-freiburg.de
authors.forename: Cedric
authors.initials: C
authors.lastname: Vonarbourg
authors.forename: Arthur
authors.initials: A
authors.lastname: Mortha
authors.forename: Viet L
authors.initials: VL
authors.lastname: Bui
authors.forename: Pedro P
authors.initials: PP
authors.lastname: Hernandez
authors.forename: Elina A
authors.initials: EA
authors.lastname: Kiss
authors.forename: Thomas
authors.initials: T
authors.lastname: Hoyler
authors.forename: Melanie
authors.initials: M
authors.lastname: Flach
authors.forename: Bertram
authors.initials: B
authors.lastname: Bengsch
authors.forename: Robert
authors.initials: R
authors.lastname: Thimme
authors.forename: Christoph
authors.initials: C
authors.lastname: Hölscher
authors.forename: Manfred
authors.initials: M
authors.lastname: Hönig
authors.forename: Ulrich
authors.initials: U
authors.lastname: Pannicke
authors.forename: Klaus
authors.initials: K
authors.lastname: Schwarz
authors.forename: Carl F
authors.initials: CF
authors.lastname: Ware
authors.forename: Daniela
authors.initials: D
authors.lastname: Finke
authors.forename: Andreas
authors.initials: A
authors.lastname: Diefenbach
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000276:immunology; D015536:Down-Regulation; D015212:Inflammatory Bowel Diseases / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D019409:Interleukin-15 / Q000276:immunology / Q000378:metabolism; D015851:Interleukin-7 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000276:immunology / Q000378:metabolism; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation; D000097043:Interleukin-22
chemical_list: D007371:Interferon-gamma; D018664:Interleukin-12; D019409:Interleukin-15; D015851:Interleukin-7; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D000097043:Interleukin-22