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.