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
Affiliations
Satoshi Hirose
Department of Surgery, Center for Neurobiology and Vaccine Development, Ophthalmology Research, Cedars-Sinai Medical Center, SSB3, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA
Pedram Shafiei Jahani
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Shaohui Wang
Department of Surgery, Center for Neurobiology and Vaccine Development, Ophthalmology Research, Cedars-Sinai Medical Center, SSB3, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA
Ujjaldeep Jaggi
Department of Surgery, Center for Neurobiology and Vaccine Development, Ophthalmology Research, Cedars-Sinai Medical Center, SSB3, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA
Kati Tormanen
Department of Surgery, Center for Neurobiology and Vaccine Development, Ophthalmology Research, Cedars-Sinai Medical Center, SSB3, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA
Jack Yu
Department of Surgery, Center for Neurobiology and Vaccine Development, Ophthalmology Research, Cedars-Sinai Medical Center, SSB3, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA
Mihoko Kato
Department of Biology, Pomona College, Claremont, CA, USA
Omid Akbari
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Homayon Ghiasi
Department of Surgery, Center for Neurobiology and Vaccine Development, Ophthalmology Research, Cedars-Sinai Medical Center, SSB3, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA; Corresponding author
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-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.
