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

Satoshi Hirose; Pedram Shafiei Jahani; Shaohui Wang; Ujjaldeep Jaggi; Kati Tormanen; Jack Yu; Mihoko Kato; Omid Akbari; Homayon Ghiasi

doi:10.1016/j.isci.2020.101549

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

iScience. 2020 Sep 10;23(10):101549. doi: 10.1016/j.isci.2020.101549. eCollection 2020 Oct 23.

Authors

Satoshi Hirose¹, Pedram Shafiei Jahani², Shaohui Wang¹, Ujjaldeep Jaggi¹, Kati Tormanen¹, Jack Yu¹, Mihoko Kato³, Omid Akbari², Homayon Ghiasi¹

Affiliations

¹ Department of Surgery, Center for Neurobiology and Vaccine Development, Ophthalmology Research, Cedars-Sinai Medical Center, SSB3, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.
² Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
³ Department of Biology, Pomona College, Claremont, CA, USA.

Abstract

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.

Keywords: Immunology; Neuroscience.

Abstract

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