CCL5 Release by CCR9+ CD8 T Cells: A Potential Contributor to Immunopathology of Primary Sjögren’s Syndrome
IntroductionIncreased CCL5 expression and CD8 T cells have been shown to be pivotal regulators of immunopathology in primary Sjögren’s syndrome (pSS) and pSS-like disease. Increased CCL5 expression by CCR9+ CD4 T cells has previously been implicated as a contributor to immunopathology in pSS. The ro...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.887972/full |
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| author | Anneline C. Hinrichs Anneline C. Hinrichs Sofie L. M. Blokland Sofie L. M. Blokland Aike A. Kruize Floris P. J. Lafeber Helen L. Leavis Joel A. G. van Roon Joel A. G. van Roon |
| author_facet | Anneline C. Hinrichs Anneline C. Hinrichs Sofie L. M. Blokland Sofie L. M. Blokland Aike A. Kruize Floris P. J. Lafeber Helen L. Leavis Joel A. G. van Roon Joel A. G. van Roon |
| author_sort | Anneline C. Hinrichs |
| collection | DOAJ |
| description | IntroductionIncreased CCL5 expression and CD8 T cells have been shown to be pivotal regulators of immunopathology in primary Sjögren’s syndrome (pSS) and pSS-like disease. Increased CCL5 expression by CCR9+ CD4 T cells has previously been implicated as a contributor to immunopathology in pSS. The role of CD8 T cells and in particular CCR9+ CD8 T cells and their potential to secrete CCL5 has not previously been studied in pSS. In this study we investigated both CCR9 and CCL5 expression by CD8 T cells in pSS patients compared to healthy controls (HC).MethodsCCR9 expression on CD8 T cells from peripheral blood was compared between patients with pSS and HC by flow cytometry. Intracellular CCL5 expression by naive, memory and effector CCR9- and CCR9+ CD8 T cells was assessed. In addition, the capacity and pace of CCL5 release upon T cell activation was determined for all subsets and compared with CD4 T cells.ResultsThe frequency of circulating CCR9+ CD8 T cells in pSS patients is increased compared to HC. Antigen-experienced CD8 T cells, especially CCR9+ effector CD8 T cells, express the highest CCL5 levels, and release the highest levels of CCL5 upon activation. Memory and effector CD8 T cells of pSS patients express significantly less CCL5 and subsequently release less CCL5 upon stimulation compared to HC. CCR9+ CD8 T cells rapidly release CCL5 and significantly more than CCR9+ CD4 T cells.ConclusionCCR9+ CD8 T cells express more CCL5 than CCR9- CD8 T cells. CCL5 is rapidly released upon activation, resulting in reduced intracellular expression. Reduced CCL5 expression by an elevated number of antigen-experienced CCR9-expressing CD8 T cells in pSS patients points towards increased release in vivo. This suggests that CCL5 release by CCR9+ CD8 T cells contributes to immunopathology in pSS. |
| first_indexed | 2024-04-12T11:12:13Z |
| format | Article |
| id | doaj.art-72a6a876f5d248908f8f6663bcfcea3a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T11:12:13Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-72a6a876f5d248908f8f6663bcfcea3a2022-12-22T03:35:35ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-06-011310.3389/fimmu.2022.887972887972CCL5 Release by CCR9+ CD8 T Cells: A Potential Contributor to Immunopathology of Primary Sjögren’s SyndromeAnneline C. Hinrichs0Anneline C. Hinrichs1Sofie L. M. Blokland2Sofie L. M. Blokland3Aike A. Kruize4Floris P. J. Lafeber5Helen L. Leavis6Joel A. G. van Roon7Joel A. G. van Roon8Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsCenter for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsDepartment of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsCenter for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsDepartment of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsDepartment of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsDepartment of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsDepartment of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsCenter for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsIntroductionIncreased CCL5 expression and CD8 T cells have been shown to be pivotal regulators of immunopathology in primary Sjögren’s syndrome (pSS) and pSS-like disease. Increased CCL5 expression by CCR9+ CD4 T cells has previously been implicated as a contributor to immunopathology in pSS. The role of CD8 T cells and in particular CCR9+ CD8 T cells and their potential to secrete CCL5 has not previously been studied in pSS. In this study we investigated both CCR9 and CCL5 expression by CD8 T cells in pSS patients compared to healthy controls (HC).MethodsCCR9 expression on CD8 T cells from peripheral blood was compared between patients with pSS and HC by flow cytometry. Intracellular CCL5 expression by naive, memory and effector CCR9- and CCR9+ CD8 T cells was assessed. In addition, the capacity and pace of CCL5 release upon T cell activation was determined for all subsets and compared with CD4 T cells.ResultsThe frequency of circulating CCR9+ CD8 T cells in pSS patients is increased compared to HC. Antigen-experienced CD8 T cells, especially CCR9+ effector CD8 T cells, express the highest CCL5 levels, and release the highest levels of CCL5 upon activation. Memory and effector CD8 T cells of pSS patients express significantly less CCL5 and subsequently release less CCL5 upon stimulation compared to HC. CCR9+ CD8 T cells rapidly release CCL5 and significantly more than CCR9+ CD4 T cells.ConclusionCCR9+ CD8 T cells express more CCL5 than CCR9- CD8 T cells. CCL5 is rapidly released upon activation, resulting in reduced intracellular expression. Reduced CCL5 expression by an elevated number of antigen-experienced CCR9-expressing CD8 T cells in pSS patients points towards increased release in vivo. This suggests that CCL5 release by CCR9+ CD8 T cells contributes to immunopathology in pSS.https://www.frontiersin.org/articles/10.3389/fimmu.2022.887972/fullprimary Sjögren’s syndrome (pSS)CCR9+ T cellsautoimmunityCCL5CD8 T cellstranscriptomics |
| spellingShingle | Anneline C. Hinrichs Anneline C. Hinrichs Sofie L. M. Blokland Sofie L. M. Blokland Aike A. Kruize Floris P. J. Lafeber Helen L. Leavis Joel A. G. van Roon Joel A. G. van Roon CCL5 Release by CCR9+ CD8 T Cells: A Potential Contributor to Immunopathology of Primary Sjögren’s Syndrome Frontiers in Immunology primary Sjögren’s syndrome (pSS) CCR9+ T cells autoimmunity CCL5 CD8 T cells transcriptomics |
| title | CCL5 Release by CCR9+ CD8 T Cells: A Potential Contributor to Immunopathology of Primary Sjögren’s Syndrome |
| title_full | CCL5 Release by CCR9+ CD8 T Cells: A Potential Contributor to Immunopathology of Primary Sjögren’s Syndrome |
| title_fullStr | CCL5 Release by CCR9+ CD8 T Cells: A Potential Contributor to Immunopathology of Primary Sjögren’s Syndrome |
| title_full_unstemmed | CCL5 Release by CCR9+ CD8 T Cells: A Potential Contributor to Immunopathology of Primary Sjögren’s Syndrome |
| title_short | CCL5 Release by CCR9+ CD8 T Cells: A Potential Contributor to Immunopathology of Primary Sjögren’s Syndrome |
| title_sort | ccl5 release by ccr9 cd8 t cells a potential contributor to immunopathology of primary sjogren s syndrome |
| topic | primary Sjögren’s syndrome (pSS) CCR9+ T cells autoimmunity CCL5 CD8 T cells transcriptomics |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.887972/full |
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