ICOS Signaling Regulates Expansion of Group 2 Innate Lymphoid Cells Under Homeostatic and Inflammatory Conditions

Group 2 innate lymphoid cells are innate effectors playing an important role in the defense against helminthic infections and in the pathogenesis of allergic inflammation. Cytokines have been identified as the major stimuli driving ILC2 activation and expansion. Conversely, it is not clear whether costimulatory molecules contribute to regulation of ILC2 functions. ILC2 display high expression of Inducible T cell costimulator (ICOS), a costimulatory molecule belonging to the CD28 superfamily, which has been shown to control late effector T cell functions, and is of upmost importance for the humoral immune response. However, the biological function of ICOS expression on ILC2 is unknown. Here we show that ICOS but not CD28 signaling regulates ILC2 homeostasis independent of T cells and B cells, by promoting proliferation and accumulation of mature ILC2 as well as their activation and expansion under inflammatory conditions. Our data identify for the first time a role of ICOS in the innate immune system and indicate that not only cytokines but also costimulatory pathways can regulate the ILC2 pool. Thus, ICOS costimulation blockade which is currently under clinical evaluation for inhibiting the humoral immune response would also enable targeting of innate inflammatory circuits.