Cytokine expression by invariant natural killer T cells is tightly regulated throughout development and settings of type-2 inflammation.
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.
Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA.
T F
TF
O'Brien
Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA.
K
K
Bao
Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA.
M
M
Dell'Aringa
Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA.
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WX
Ang
Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA.
S
S
Abraham
Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA.
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RL
Reinhardt
D000818:Animals; D001249:Asthma / Q000276:immunology*; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism*; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology*; D039981:Pyroglyphidae / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
D018793:Interleukin-13; D015847:Interleukin-4