Sphingosine Kinase 2 mediates LCMV-induced CD4(+) T cell suppression and instigates viral persistence while preventing immunopathology
DC Field | Value | Language |
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dc.contributor.author | Studstill, Caleb J. | - |
dc.contributor.author | Pritzl, Curtis J. | - |
dc.contributor.author | Seo, Young-Jin | - |
dc.contributor.author | Kim, Dae Y. | - |
dc.contributor.author | Xia, Chuan Z. | - |
dc.contributor.author | Wolf, Jennifer J. | - |
dc.contributor.author | Vijayan, Madhuvanthi | - |
dc.contributor.author | Hahm, Bumsuk | - |
dc.date.accessioned | 2022-01-24T03:42:58Z | - |
dc.date.available | 2022-01-24T03:42:58Z | - |
dc.date.issued | 2019-05 | - |
dc.identifier.issn | 0022-1767 | - |
dc.identifier.issn | 1550-6606 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/54186 | - |
dc.description.abstract | Viruses often establish persistent infections by causing dysfunctional T cell responses. Little is known about the role of sphingosine kinase 2 (SphK2) in the immune response to viral infections; even though, its enzymatic product, sphingosine 1-phosphate, is well-known to regulate versatile cellular processes. In this work, we demonstrate that during lymphocytic choriomeningitis virus clone 13 (LCMV Cl 13) infection in mice, SphK2 functions to limit CD4+ T cell responses, which aids in the establishment of virus-induced immunosuppression and viral persistence. The infection of SphK2-deficient (SphK2−/−) mice with LCMV Cl 13 resulted in kidney disease and ultimately mortality, which was not observed with acute infection by the Armstrong strain of LCMV. Following infection, SphK2−/− mice were shown to have increased LCMV-specific CD4+ and CD8+ T cell responses. Depletion of CD4+ or CD8+ T cells prevented the infection-induced death of SphK2−/− mice, which indicates T cell-mediated immunopathology. With the use of LCMV epitope-specific TCR transgenic mouse lines for adoptive transfer studies, SphK2 was shown to have intrinsic negative function in CD4+ T cells, but not CD8+ T cells. Furthermore, SphK2−/− CD4+ T cells were able to promote endogenous, virus-specific CD8+ T cell responses. Importantly, oral treatment of LCMV Cl 13-infected mice with an SphK2-selective inhibitor increased the number of LCMV-reactive CD4+ and CD8+ T cells, and led to the accelerated termination of LCMV Cl 13 persistence, without causing mortality. Our results suggest that transient SphK2 inhibition is a promising novel immunotherapeutic strategy for the control of persistent viral infections. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | American Association of Immunologists | - |
dc.title | Sphingosine Kinase 2 mediates LCMV-induced CD4(+) T cell suppression and instigates viral persistence while preventing immunopathology | - |
dc.type | Article | - |
dc.identifier.doi | 10.4049/jimmunol.202.Supp.197.5 | - |
dc.identifier.bibliographicCitation | Journal of Immunology, v.202, no.sup.1 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000524982502116 | - |
dc.citation.number | sup.1 | - |
dc.citation.title | Journal of Immunology | - |
dc.citation.volume | 202 | - |
dc.type.docType | Meeting Abstract | - |
dc.publisher.location | 미국 | - |
dc.relation.journalResearchArea | Immunology | - |
dc.relation.journalWebOfScienceCategory | Immunology | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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