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

ABSTRACT: Summary 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-2r??/?, IL-2r??/?, and IL-2r??/? mice showed demyelination in the CNS of IL-2r??/? and IL-2r??/? mice but not in the CNS of IL-2r??/?-infected mice. No demyelination was detected in mice infected with control virus. IL-2r??/? 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. Graphical Abstract Highlights • IL-2r??/?, but not IL-2r??/? or IL-2r??/?, mice are protected from CNS demyelination• Mice lacking ILC2s, but not ILC1s or ILC3s, are protected from CNS demyelination• Transfer of ILC2s from WT to ILC2?/? mice restore CNS demyelination to infected mice• Suppression of CCL5 and CXCL10 correlated with CNS demyelination Immunology; Neuroscience

SUBMITTER: Hirose S

PROVIDER: S-EPMC7522755 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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