title: The transcription factor T-bet is essential for the development of NKp46+ innate lymphocytes via the Notch pathway.
abstract: NKp46+ innate lymphoid cells (ILCs) serve important roles in regulating the intestinal microbiota and defense against pathogens. Whether NKp46+ ILCs arise directly from lymphoid tissue-inducer (LTi) cells or represent a separate lineage remains controversial. We report here that the transcription factor T-bet (encoded by Tbx21) was essential for the development of NKp46+ ILCs but not of LTi cells or nuocytes. Deficiency in interleukin 22 (IL-22)-producing NKp46+ ILCs resulted in greater susceptibility of Tbx21-/- mice to intestinal infection. Haploinsufficient T-bet expression resulted in lower expression of the signaling molecule Notch, and Notch signaling was necessary for the transition of LTi cells into NKp46+ ILCs. Furthermore, NKp46+ ILCs differentiated solely from the CD4- LTi population, not the CD4+ LTi population. Our results pinpoint the regulation of Notch signaling by T-bet as a distinct molecular pathway that guides the development of NKp46+ ILCs.
authors: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
authors: Lucille C
authors: LC
authors: Rankin
authors: Joanna R
authors: JR
authors: Groom
authors: Michaël
authors: M
authors: Chopin
authors: Marco J
authors: MJ
authors: Herold
authors: Jennifer A
authors: JA
authors: Walker
authors: Lisa A
authors: LA
authors: Mielke
authors: Andrew N J
authors: AN
authors: McKenzie
authors: Sebastian
authors: S
authors: Carotta
authors: Stephen L
authors: SL
authors: Nutt
authors: Gabrielle T
authors: GT
authors: Belz
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D044082:Citrobacter rodentium / Q000276:immunology; D004756:Enterobacteriaceae Infections / Q000276:immunology; D007113:Immunity, Innate; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D000098815:T-bet Transcription Factor
chemical_list: D000950:Antigens, Ly; D055627:Natural Cytotoxicity Triggering Receptor 1; C118384:Ncr1 protein, mouse; D051880:Receptors, Notch; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor