Defining iNKT cell subpopulations

This study clarifies our view of the heterogeneity of invariant natural killer T (iNKT) cells by defining the development and functional properties of distinct subsets in mice. Interleukin-17 receptor B (IL-17RB)-expressing iNKT cells produce the T helper 2 (T_H2)-type cytokines IL-9, IL-10 and IL-13 and the T_H17-type cytokines IL-17A and IL-22, whereas IL-17RB⁻ iNKT cells produce mainly the T_H1-type cytokine interferon-γ. IL-17RB⁺ and IL-17RB⁻ iNKT cell subsets were shown to develop independently in the thymus. Further studies showed three distinct iNKT cell subpopulations in the thymus: IL-23-responsive CD4⁻IL-17RB⁺ cells that produce T_H17-type cytokines; IL-25-responsive CD4⁺IL-17RB⁺ cells that produce T_H2- and T_H17-type cytokines; and IL-12-responsive CD4⁺ or CD4⁻ IL-17RB⁻ cells that produce T_H1-type cytokines. These populations also exist as phenotypically and functionally distinct subtypes with different distribution patterns in the periphery, and it will be interesting to determine their differential roles in pathological conditions.