Type 2 Innate Lymphoid Cells Induce CNS Demyelination in an HSV-IL-2 Mouse Model of Multiple Sclerosis

We previously reported that infection of different mouse strains with a recombinant HSV-1 expressing IL-2 (HSV-IL-2) caused CNS demyelination. Histologic examination of infected IL-2rα(−/−), IL-2rβ(−/−), and IL-2rγ(−/−) mice showed demyelination in the CNS of IL-2rα(−/−) and IL-2rβ(−/−) mice but not in the CNS of IL-2rγ(−/−)-infected mice. No demyelination was detected in mice infected with control virus. IL-2rγ(−/−) mice that lack type 2 innate lymphoid cells (ILC2s) and ILCs, play important roles in host defense and inflammation. We next infected ILC1(−/−), ILC2(−/−), and ILC3(−/−) mice with HSV-IL-2 or wild-type (WT) HSV-1. In contrast to ILC1(−/−) and ILC3(−/−) mice, no demyelination was detected in the CNS of ILC2(−/−)-sinfected mice. However, transfer of ILC2s from WT mice to ILC2(−/−) mice restored demyelination in infected recipient mice. CNS demyelination correlated with downregulation of CCL5 and CXCL10. This study demonstrates that ILC2s contribute to HSV-IL-2-induced CNS demyelination in a mouse model of multiple sclerosis.