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Mucosal Immunol. 2016 May;9(3):597-609. doi: 10.1038/mi.2015.78. Epub 2015 Sep 9.

Cytokine expression by invariant natural killer T cells is tightly regulated throughout development and settings of type-2 inflammation.

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Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA.
Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA.


Invariant natural killer T (iNKT) cells produce cytokines interleukin-4 (IL-4) and IL-13 during type-2 inflammatory responses. However, the nature in which iNKT cells acquire type-2 cytokine competency and the precise contribution of iNKT cell-derived IL-4 and IL-13 in vivo remains unclear. Using IL-13-reporter mice to fate-map cytokine-expressing cells in vivo, this study reveals that thymic iNKT cells express IL-13 early during development, and this IL-13-expressing intermediate gives rise to mature iNKT1, iNKT2, and iNKT17 subsets. IL-4 and IL-13 reporter mice also reveal that effector iNKT2 cells produce IL-4 but little IL-13 in settings of type-2 inflammation. The preferential production of IL-4 over IL-13 in iNKT2 cells results in part from their reduced GATA-3 expression. In summary, this work helps integrate current models of iNKT cell development, and further establishes non-coordinate production of IL-4 and IL-13 as the predominant pattern of type-2 cytokine expression among innate cells in vivo.

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