title: Id2 regulates hyporesponsive invariant natural killer T cells.
abstract: While the invariant natural killer T (iNKT)-cell response to primary stimulation with the glycolipid, α-galactosylceramide (αGalCer), is robust, the secondary response to this stimulus is muted resulting in a hyporesponsive state characterized by anti-inflammatory interleukin-10 (IL-10) production and high expression of programmed cell death 1 (PD1) and neuropilin 1 (NRP1). The E protein transcription factors and their negative regulators, the Id proteins, have previously been shown to regulate iNKT cell thymic development, subset differentiation and peripheral survival. Here, we provide evidence that the expression of the transcriptional regulator Id2 is downregulated upon stimulation of iNKT cells with their cognate antigen. Moreover, loss of Id2 expression by iNKT cells resulted in a hyporesponsive state, with splenic Id2-deficient iNKT cells expressing low levels of TBET, high levels of PD1 and NRP1 and production of IL-10 upon stimulation. We propose that downregulation of Id2 expression is an essential component of induction of the anti-inflammatory, hyporesponsive state in iNKT cells.
authors.affiliation: Division of Rheumatology and Immunology, Medical University of Graz, Graz, Austria.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Stradner
authors.affiliation: Division of Biology, University of California San Diego, La Jolla, CA, USA.
authors.forename: Kitty P
authors.initials: KP
authors.lastname: Cheung
authors.affiliation: Department of Pediatrics and Pathology and Cell Biology, Columbia University, New York, NY, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Lasorella
authors.affiliation: Division of Biology, University of California San Diego, La Jolla, CA, USA.
authors.forename: Ananda W
authors.initials: AW
authors.lastname: Goldrath
authors.affiliation: Department of Immunology, University of Pittsburgh, Biomedical Science Tower, Pittsburgh, PA, USA.
authors.forename: Louise M
authors.initials: LM
authors.lastname: D'Cruz
mesh_terms: D000818:Animals; D015536:Down-Regulation; D051797:Inhibitor of Differentiation Protein 2 / Q000378:metabolism*; D051379:Mice; D055611:Natural Killer T-Cells / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology
chemical_list: C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D011948:Receptors, Antigen, T-Cell