title: Development and function of invariant natural killer T cells producing T(h)2- and T(h)17-cytokines.
abstract: There is heterogeneity in invariant natural killer T (iNKT) cells based on the expression of CD4 and the IL-17 receptor B (IL-17RB), a receptor for IL-25 which is a key factor in T(H)2 immunity. However, the development pathway and precise function of these iNKT cell subtypes remain unknown. IL-17RB⁺iNKT cells are present in the thymic CD44⁺/⁻ NK1.1⁻ population and develop normally even in the absence of IL-15, which is required for maturation and homeostasis of IL-17RB⁻iNKT cells producing IFN-γ. These results suggest that iNKT cells contain at least two subtypes, IL-17RB⁺ and IL-17RB⁻ subsets. The IL-17RB⁺iNKT subtypes can be further divided into two subtypes on the basis of CD4 expression both in the thymus and in the periphery. CD4⁺ IL-17RB⁺iNKT cells produce T(H)2 (IL-13), T(H)9 (IL-9 and IL-10), and T(H)17 (IL-17A and IL-22) cytokines in response to IL-25 in an E4BP4-dependent fashion, whereas CD4⁻ IL-17RB⁺iNKT cells are a retinoic acid receptor-related orphan receptor (ROR)γt⁺ subset producing T(H)17 cytokines upon stimulation with IL-23 in an E4BP4-independent fashion. These IL-17RB⁺iNKT cell subtypes are abundantly present in the lung in the steady state and mediate the pathogenesis in virus-induced airway hyperreactivity (AHR). In this study we demonstrated that the IL-17RB⁺iNKT cell subsets develop distinct from classical iNKT cell developmental stages in the thymus and play important roles in the pathogenesis of airway diseases.
authors.affiliation: Laboratory for Immune Regulation, RIKEN Research Center for Allergy and Immunology, Kanagawa, Japan. hwatarai@rcai.riken.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watarai
authors.forename: Etsuko
authors.initials: E
authors.lastname: Sekine-Kondo
authors.forename: Tomokuni
authors.initials: T
authors.lastname: Shigeura
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Motomura
authors.forename: Takuwa
authors.initials: T
authors.lastname: Yasuda
authors.forename: Rumi
authors.initials: R
authors.lastname: Satoh
authors.forename: Hisahiro
authors.initials: H
authors.lastname: Yoshida
authors.forename: Masato
authors.initials: M
authors.lastname: Kubo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawamoto
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
mesh_terms: D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D016130:Immunophenotyping; D008099:Liver / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000473:pathology / Q000502:physiology*; D009928:Organ Specificity; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000378:metabolism / Q000502:physiology*; D058504:Th17 Cells / Q000473:pathology / Q000502:physiology; D018418:Th2 Cells / Q000473:pathology / Q000502:physiology; D013950:Thymus Gland / Q000473:pathology; D046509:Tissue Culture Techniques
chemical_list: D016207:Cytokines; D053722:Receptors, Interleukin-17