Expression of c‐Kit discriminates between two functionally distinct subsets of human type 2 innate lymphoid cells

Abstract

Human type 2 innate lymphoid cells (ILC2) are the only ILC subset that shows heterogeneous expression of the SCF receptor c‐Kit (CD117). Despite its use as surface marker to distinguish ILC populations, its influence on ILC2 biology has not been investigated. Here, we show that c‐Kit expression of peripheral blood ILC distinguishes two functionally distinct ILC2 subsets (c‐Kithi and c‐Kitlo). When examined for their potential for functional plasticity we found that c‐Kitlo ILC2 displayed greater potential to produce type 2 cytokines, possibly representing fully mature and lineage committed ILC2. On the other hand, c‐Kithi ILC2 coexpressed the ILC3‐marker and chemokine receptor CCR6 and were able to mount a significant IL‐17A response under ILC3‐promoting conditions. In addition, c‐Kithi ILC2 produced higher levels of IFN‐γ than c‐Kitlo ILC2 under ILC1‐conditions. Although costimulation with SCF did not further influence ILC2 plasticity, it augmented type 2 cytokine production. We conclude that c‐Kit marks distinct subpopulations of ILC2, which has therapeutic implications for conditions in which ILC2 are involved, such as allergy and asthma.