Progressive loss of RORγt expression confers distinct functional fates to natural killer cell receptor-expressing RORγt+ innate lymphocytes

By C. Vonarbourg, A. Mortha, Viet L Bui, Pedro P. Hernández, E. A. Kiss, T. Hoyler, Melanie Flach, B. Bengsch, R. Thimme, C. Hölscher and 6 more. Immunity, 2010

666 citations recorded by the source corpus.

Summary Whether the recently identified innate lymphocyte population co-expressing natural killer cell receptors (NKRs) and the nuclear receptor RORγt is part of the NK or lymphoid tissue inducer (LTi) cell lineage remains unclear. 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.

Subfields: Immunology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/6d34a7237100b9d49675de31b5e6a10a07b347ec

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In Immunology

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In Pathology and Forensic Medicine

1. F. Powrie
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Citations in the corpus

• Border patrol: regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22 (2011, background): “IL-22-producing ILCs are responsive to common γ-chain cytokines, such as IL-7, which can promote the expansion of various ILC population”
• Cytokine Networks in the Pathophysiology of Inflammatory Bowel Disease. (2019, background): “RORyt- ILC1s drive colitis through production of IFN-γ (Powell et al., 2012; Vonarbourg et al., 2010).”
• AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch (2011, background): “Whether NKp46 + ILCs are the progeny of LTi-like ILCs or a closely related cell lineage has been matter of debat”
• The Aryl Hydrocarbon Receptor Regulates Gut Immunity through Modulation of Innate Lymphoid Cells (2011, background): “IL-7 signaling pathway has been shown to stabilize RORgt expression in ILCs and may be required for survival and maintenance of RORgt ILCs (Meier et al., 2007; Vonarbourg et al., 2010).”
• Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161 (2011, background): “Published evidence suggests that RORγt expression is not always stable; in RORγt reporter mice, downregulation of RORγt is associated with a functional shift from IL-22 production to IFN-γ productio”