IL-6 and IL-27 play both distinct and redundant roles in regulating CD4 T-cell responses during chronic viral infection
The IL-6 cytokine family signals through the common signal transduction molecule gp130 combined with a cytokine-specific receptor. Gp130 signaling on CD4 T cells is vital in controlling chronic infection of mice with lymphocytic choriomeningitis virus clone 13 (LCMV Cl13), but the precise role of in...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1221562/full |
| _version_ | 1827889391087910912 |
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| author | James A. Harker James A. Harker Trever T. Greene Burton E. Barnett Phuc Bao Aleksandr Dolgoter Elina I. Zuniga |
| author_facet | James A. Harker James A. Harker Trever T. Greene Burton E. Barnett Phuc Bao Aleksandr Dolgoter Elina I. Zuniga |
| author_sort | James A. Harker |
| collection | DOAJ |
| description | The IL-6 cytokine family signals through the common signal transduction molecule gp130 combined with a cytokine-specific receptor. Gp130 signaling on CD4 T cells is vital in controlling chronic infection of mice with lymphocytic choriomeningitis virus clone 13 (LCMV Cl13), but the precise role of individual members of the IL-6 cytokine family is not fully understood. Transcriptional analysis highlighted the importance of gp130 signaling in promoting key processes in CD4 T cells after LCMV Cl13 infection, particularly genes associated with T follicular helper (Tfh) cell differentiation and IL-21 production. Further, Il27r−/−Il6ra−/− mice failed to generate antibody or CD8 T-cell immunity and to control LCMV Cl13. Transcriptomics and phenotypic analyses of Il27r−/−Il6ra−/− Tfh cells revealed that IL-6R and IL-27R signaling was required to activate key pathways within CD4 T cells. IL-6 and IL-27 signaling has distinct and overlapping roles, with IL-6 regulating Tfh differentiation, IL-27 regulating CD4 T cell survival, and both redundantly promoting IL-21. |
| first_indexed | 2024-03-12T20:55:59Z |
| format | Article |
| id | doaj.art-50f2afff8074497a9c4c07c1865892ed |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T20:55:59Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-50f2afff8074497a9c4c07c1865892ed2023-07-31T16:10:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-07-011410.3389/fimmu.2023.12215621221562IL-6 and IL-27 play both distinct and redundant roles in regulating CD4 T-cell responses during chronic viral infectionJames A. Harker0James A. Harker1Trever T. Greene2Burton E. Barnett3Phuc Bao4Aleksandr Dolgoter5Elina I. Zuniga6Division of Molecular Biology, Department of Biological Sciences, University of California San Diego, La Jolla, CA, United StatesNational Heart and Lung Institute, Imperial College London, London, United KingdomDivision of Molecular Biology, Department of Biological Sciences, University of California San Diego, La Jolla, CA, United StatesDivision of Molecular Biology, Department of Biological Sciences, University of California San Diego, La Jolla, CA, United StatesDivision of Molecular Biology, Department of Biological Sciences, University of California San Diego, La Jolla, CA, United StatesDivision of Molecular Biology, Department of Biological Sciences, University of California San Diego, La Jolla, CA, United StatesDivision of Molecular Biology, Department of Biological Sciences, University of California San Diego, La Jolla, CA, United StatesThe IL-6 cytokine family signals through the common signal transduction molecule gp130 combined with a cytokine-specific receptor. Gp130 signaling on CD4 T cells is vital in controlling chronic infection of mice with lymphocytic choriomeningitis virus clone 13 (LCMV Cl13), but the precise role of individual members of the IL-6 cytokine family is not fully understood. Transcriptional analysis highlighted the importance of gp130 signaling in promoting key processes in CD4 T cells after LCMV Cl13 infection, particularly genes associated with T follicular helper (Tfh) cell differentiation and IL-21 production. Further, Il27r−/−Il6ra−/− mice failed to generate antibody or CD8 T-cell immunity and to control LCMV Cl13. Transcriptomics and phenotypic analyses of Il27r−/−Il6ra−/− Tfh cells revealed that IL-6R and IL-27R signaling was required to activate key pathways within CD4 T cells. IL-6 and IL-27 signaling has distinct and overlapping roles, with IL-6 regulating Tfh differentiation, IL-27 regulating CD4 T cell survival, and both redundantly promoting IL-21.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1221562/fullchronic viral infectionlcmvIL-6IL-27T follicular helper cells |
| spellingShingle | James A. Harker James A. Harker Trever T. Greene Burton E. Barnett Phuc Bao Aleksandr Dolgoter Elina I. Zuniga IL-6 and IL-27 play both distinct and redundant roles in regulating CD4 T-cell responses during chronic viral infection Frontiers in Immunology chronic viral infection lcmv IL-6 IL-27 T follicular helper cells |
| title | IL-6 and IL-27 play both distinct and redundant roles in regulating CD4 T-cell responses during chronic viral infection |
| title_full | IL-6 and IL-27 play both distinct and redundant roles in regulating CD4 T-cell responses during chronic viral infection |
| title_fullStr | IL-6 and IL-27 play both distinct and redundant roles in regulating CD4 T-cell responses during chronic viral infection |
| title_full_unstemmed | IL-6 and IL-27 play both distinct and redundant roles in regulating CD4 T-cell responses during chronic viral infection |
| title_short | IL-6 and IL-27 play both distinct and redundant roles in regulating CD4 T-cell responses during chronic viral infection |
| title_sort | il 6 and il 27 play both distinct and redundant roles in regulating cd4 t cell responses during chronic viral infection |
| topic | chronic viral infection lcmv IL-6 IL-27 T follicular helper cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1221562/full |
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