Induced IL-17–Producing Invariant NKT Cells Require Activation in Presence of TGF-β and IL-1β

IL-17 production by innate-like lymphocytes, including γδ and invariant NKT (iNKT) cells, have been ascribed to specific lineages that are endowed with this functional specialization during thymic differentiation. IL-17-producing iNKT cells have been described as a CD4(-)NK1.1(-) lineage in mice and CD161(+) in humans. We found that, in mice, noncommitted iNKT cells can be induced to produce IL-17 when activated in presence of TGF-β and IL-1β. This peripheral induction of IL-17 expression could be observed in any subset irrespectively of CD4 and NK1.1 expression, the process leading to loss of NK1.1 expression and partial CD4 downmodulation. Furthermore, induced IL-17-producing iNKT cells were sufficient to drive neutrophilic airways inflammation upon intratracheal adoptive cell transfer into congenic mice. Taken together, our data show that similarly to regulatory T cells, which have a natural and peripherally induced subset, IL-17 production by iNKT cells can also be imprinted in natural iNKT17 cells or peripherally induced.