IL-17A expression by both T cells and non-T cells contribute to HSV-IL-2-induced CNS demyelination
Previously we reported that a recombinant HSV-1 expressing murine IL-2 (HSV-IL-2) causes CNS demyelination in different strains of mice and in a T cell-dependent manner. Since TH17 cells have been implicated in CNS pathology, in the present study, we looked into the effects of IL-17A-/- and three of...
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| Format: | Article |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1102486/full |
| _version_ | 1797936104070971392 |
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| author | Satoshi Hirose Shaohui Wang Ujjaldeep Jaggi Harry H. Matundan Mihoko Kato Xue-Ying Song Sara J. Molesworth-Kenyon Robert N. Lausch Homayon Ghiasi |
| author_facet | Satoshi Hirose Shaohui Wang Ujjaldeep Jaggi Harry H. Matundan Mihoko Kato Xue-Ying Song Sara J. Molesworth-Kenyon Robert N. Lausch Homayon Ghiasi |
| author_sort | Satoshi Hirose |
| collection | DOAJ |
| description | Previously we reported that a recombinant HSV-1 expressing murine IL-2 (HSV-IL-2) causes CNS demyelination in different strains of mice and in a T cell-dependent manner. Since TH17 cells have been implicated in CNS pathology, in the present study, we looked into the effects of IL-17A-/- and three of its receptors on HSV-IL-2-induced CNS demyelination. IL-17A-/- mice did not develop CNS demyelination, while IL-17RA-/-, IL-17RC-/-, IL-17RD-/- and IL-17RA-/-RC-/- mice developed CNS demyelination. Adoptive transfer of T cells from wild-type (WT) mice to IL-17A-/- mice or T cells from IL-17A-/- mice to Rag-/- mice induced CNS demyelination in infected mice. Adoptive T cell experiments suggest that both T cells and non-T cells expressing IL-17A contribute to HSV-IL-2-induced CNS demyelination with no difference in the severity of demyelination between the two groups of IL-17A producing cells. IL-6, IL-10, or TGFβ did not contribute to CNS demyelination in infected mice. Transcriptome analysis between IL-17A-/- brain and spinal cord of infected mice with and without T cell transfer from WT mice revealed that “neuron projection extension involved in neuron projection guidance” and “ensheathment of neurons” pathways were associated with CNS demyelination. Collectively, the results indicate the importance of IL-17A in CNS demyelination and the possible involvement of more than three of IL-17 receptors in CNS demyelination. |
| first_indexed | 2024-04-10T18:24:33Z |
| format | Article |
| id | doaj.art-6dec023a402c4ed3b35b88e5581101fd |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T18:24:33Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-6dec023a402c4ed3b35b88e5581101fd2023-02-02T06:07:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-02-011410.3389/fimmu.2023.11024861102486IL-17A expression by both T cells and non-T cells contribute to HSV-IL-2-induced CNS demyelinationSatoshi Hirose0Shaohui Wang1Ujjaldeep Jaggi2Harry H. Matundan3Mihoko Kato4Xue-Ying Song5Sara J. Molesworth-Kenyon6Robert N. Lausch7Homayon Ghiasi8Center for Neurobiology & Vaccine Development, Ophthalmology Research, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesCenter for Neurobiology & Vaccine Development, Ophthalmology Research, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesCenter for Neurobiology & Vaccine Development, Ophthalmology Research, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesCenter for Neurobiology & Vaccine Development, Ophthalmology Research, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesDepartment of Biology, Pomona College, Claremont, CA, United StatesApplied Genomics, Computation, and Translational Core, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesDepartment of Natural Sciences, University of West Georgia, Carrollton, GA, United StatesDepartment of Microbiology and Immunology, University of South Alabama, College of Medicine, Mobile, Al, United StatesCenter for Neurobiology & Vaccine Development, Ophthalmology Research, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesPreviously we reported that a recombinant HSV-1 expressing murine IL-2 (HSV-IL-2) causes CNS demyelination in different strains of mice and in a T cell-dependent manner. Since TH17 cells have been implicated in CNS pathology, in the present study, we looked into the effects of IL-17A-/- and three of its receptors on HSV-IL-2-induced CNS demyelination. IL-17A-/- mice did not develop CNS demyelination, while IL-17RA-/-, IL-17RC-/-, IL-17RD-/- and IL-17RA-/-RC-/- mice developed CNS demyelination. Adoptive transfer of T cells from wild-type (WT) mice to IL-17A-/- mice or T cells from IL-17A-/- mice to Rag-/- mice induced CNS demyelination in infected mice. Adoptive T cell experiments suggest that both T cells and non-T cells expressing IL-17A contribute to HSV-IL-2-induced CNS demyelination with no difference in the severity of demyelination between the two groups of IL-17A producing cells. IL-6, IL-10, or TGFβ did not contribute to CNS demyelination in infected mice. Transcriptome analysis between IL-17A-/- brain and spinal cord of infected mice with and without T cell transfer from WT mice revealed that “neuron projection extension involved in neuron projection guidance” and “ensheathment of neurons” pathways were associated with CNS demyelination. Collectively, the results indicate the importance of IL-17A in CNS demyelination and the possible involvement of more than three of IL-17 receptors in CNS demyelination.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1102486/fullOcular infectionmouseHSV-IL-2knockoutIL17RAIL17RC |
| spellingShingle | Satoshi Hirose Shaohui Wang Ujjaldeep Jaggi Harry H. Matundan Mihoko Kato Xue-Ying Song Sara J. Molesworth-Kenyon Robert N. Lausch Homayon Ghiasi IL-17A expression by both T cells and non-T cells contribute to HSV-IL-2-induced CNS demyelination Frontiers in Immunology Ocular infection mouse HSV-IL-2 knockout IL17RA IL17RC |
| title | IL-17A expression by both T cells and non-T cells contribute to HSV-IL-2-induced CNS demyelination |
| title_full | IL-17A expression by both T cells and non-T cells contribute to HSV-IL-2-induced CNS demyelination |
| title_fullStr | IL-17A expression by both T cells and non-T cells contribute to HSV-IL-2-induced CNS demyelination |
| title_full_unstemmed | IL-17A expression by both T cells and non-T cells contribute to HSV-IL-2-induced CNS demyelination |
| title_short | IL-17A expression by both T cells and non-T cells contribute to HSV-IL-2-induced CNS demyelination |
| title_sort | il 17a expression by both t cells and non t cells contribute to hsv il 2 induced cns demyelination |
| topic | Ocular infection mouse HSV-IL-2 knockout IL17RA IL17RC |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1102486/full |
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