Development and function of invariant natural killer T cells producing T H2- and T H17-cytokines

Hiroshi Watarai, Etsuko Sekine-Kondo, Tomokuni Shigeura, Yasutaka Motomura, Takuwa Yasuda, Rumi Satoh, Hisahiro Yoshida, Masato Kubo, Hiroshi Kawamoto, Haruhiko Koseki, Masaru Taniguchi

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154 Citations (Scopus)


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 H2 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 H2 (IL-13), T H9 (IL-9 and IL-10), and T H17 (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 H17 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.

Original languageEnglish
Article numbere1001255
JournalPLoS Biology
Issue number2
Publication statusPublished - 02-2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)


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