title: Temporal regulation of Wnt/β-catenin signaling is important for invariant NKT cell development and terminal maturation.
abstract: The Wnt/β-catenin signaling pathway plays important roles during various cellular functions including survival and proliferation of immune cells. The critical role of this pathway in conventional T cell development is established but little is known about its contributions to innate T cell development. In this study, we found that β-catenin level, an indication of the strength of Wnt/β-catenin signaling, is regulated during invariant NKT (iNKT) cell development. β-catenin levels were greatly increased during iNKT cell selection from double positive thymocytes to Stage 0 of iNKT cell development and during subsequent development to Stage 1. Thereafter, β-catenin levels decrease from Stage 2, which is essential for the terminal maturation of iNKT cells. Failure to dampen Wnt/β-catenin signaling as in mice expressing a stabilized active form of β-catenin (CATtg) resulted in increased Stage 2 and decreased Stage 3 iNKT cells. Inefficient transition from Stage 2 to 3 in CATtg iNKT cells seems to be contributed by poor expression of IL-15R (CD122) and transcription factor T-bet, both of which are necessary for terminal maturation of iNKT cells in the thymus. Consequently, IFN-γ+ iNKT cells were greatly reduced in CATtg mice. Together, our findings reveal that proper regulation of β-catenin and in turn Wnt signaling plays an important role in the terminal maturation and function of iNKT cells.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Kalyani
authors.initials: K
authors.lastname: Pyaram
authors.affiliation: National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA; Department of Medicine, The John Hopkins University School of Medicine, Baltimore, MD 217287, USA.
authors.forename: Jyoti Misra
authors.initials: JM
authors.lastname: Sen
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address: heechang@umich.edu.
authors.forename: Cheong-Hee
authors.initials: CH
authors.lastname: Chang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D060449:Wnt Signaling Pathway / Q000276:immunology*
keywords: CD122; Cytokines; PLZF; Wnt/β-catenin; iNKT cell development