IL-27 shapes the immune properties of human astrocytes and their impact on encountered human T lymphocytes
Abstract Background Interleukin-27 (IL-27) can trigger both pro- and anti-inflammatory responses. This cytokine is elevated in the central nervous system (CNS) of multiple sclerosis (MS) patients, but how it influences neuroinflammatory processes remains unclear. As astrocytes express the receptor f...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-022-02572-1 |
| _version_ | 1798004317007904768 |
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| author | Florent Lemaître Negar Farzam-kia Ana Carmena Moratalla Yves Carpentier Solorio Marie-Laure Clenet Olivier Tastet Aurélie Cleret-Buhot Jean Victor Guimond Elie Haddad Pierre Duquette J. Marc Girard Alexandre Prat Catherine Larochelle Nathalie Arbour |
| author_facet | Florent Lemaître Negar Farzam-kia Ana Carmena Moratalla Yves Carpentier Solorio Marie-Laure Clenet Olivier Tastet Aurélie Cleret-Buhot Jean Victor Guimond Elie Haddad Pierre Duquette J. Marc Girard Alexandre Prat Catherine Larochelle Nathalie Arbour |
| author_sort | Florent Lemaître |
| collection | DOAJ |
| description | Abstract Background Interleukin-27 (IL-27) can trigger both pro- and anti-inflammatory responses. This cytokine is elevated in the central nervous system (CNS) of multiple sclerosis (MS) patients, but how it influences neuroinflammatory processes remains unclear. As astrocytes express the receptor for IL-27, we sought to determine how these glial cells respond to this cytokine and whether such exposure alters their interactions with infiltrating activated T lymphocytes. To determine whether inflammation shapes the impact of IL-27, we compared the effects of this cytokine in non-inflamed and inflamed conditions induced by an IL-1β exposure. Main body Transcriptomic analysis of IL-27-exposed human astrocytes showed an upregulation of multiple immune genes. Human astrocytes increased the secretion of chemokines (CXCL9, CXCL10, and CXCL11) and the surface expression of proteins (PD-L1, HLA-E, and ICAM-1) following IL-27 exposure. To assess whether exposure of astrocytes to IL-27 influences the profile of activated T lymphocytes infiltrating the CNS, we used an astrocyte/T lymphocyte co-culture model. Activated human CD4+ or CD8+ T lymphocytes were co-cultured with astrocytes that have been either untreated or pre-exposed to IL‑27 or IL-1β. After 24 h, we analyzed T lymphocytes by flow cytometry for transcription factors and immune molecules. The contact with IL-27-exposed astrocytes increased the percentages of T-bet, Eomes, CD95, IL-18Rα, ICAM-1, and PD-L1 expressing CD4+ and CD8+ T lymphocytes and reduced the proportion of CXCR3-positive CD8+ T lymphocytes. Human CD8+ T lymphocytes co-cultured with human IL-27-treated astrocytes exhibited higher motility than when in contact with untreated astrocytes. These results suggested a preponderance of kinapse-like over synapse-like interactions between CD8+ T lymphocytes and IL-27-treated astrocytes. Finally, CD8+ T lymphocytes from MS patients showed higher motility in contact with IL-27-exposed astrocytes compared to healthy donors’ cells. Conclusion Our results establish that IL-27 alters the immune functions of human astrocytes and shapes the profile and motility of encountered T lymphocytes, especially CD8+ T lymphocytes from MS patients. |
| first_indexed | 2024-04-11T12:21:33Z |
| format | Article |
| id | doaj.art-8434c3d5adf64a639e4ad26980f36437 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-04-11T12:21:33Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-8434c3d5adf64a639e4ad26980f364372022-12-22T04:24:04ZengBMCJournal of Neuroinflammation1742-20942022-09-0119111610.1186/s12974-022-02572-1IL-27 shapes the immune properties of human astrocytes and their impact on encountered human T lymphocytesFlorent Lemaître0Negar Farzam-kia1Ana Carmena Moratalla2Yves Carpentier Solorio3Marie-Laure Clenet4Olivier Tastet5Aurélie Cleret-Buhot6Jean Victor Guimond7Elie Haddad8Pierre Duquette9J. Marc Girard10Alexandre Prat11Catherine Larochelle12Nathalie Arbour13Department of Neurosciences, Université de Montréal and Centre de Recherche du CHUM (CRCHUM)Department of Neurosciences, Université de Montréal and Centre de Recherche du CHUM (CRCHUM)Department of Neurosciences, Université de Montréal and Centre de Recherche du CHUM (CRCHUM)Department of Neurosciences, Université de Montréal and Centre de Recherche du CHUM (CRCHUM)Department of Neurosciences, Université de Montréal and Centre de Recherche du CHUM (CRCHUM)Department of Neurosciences, Université de Montréal and Centre de Recherche du CHUM (CRCHUM)Centre de Recherche du Centre Hospitalier de L’Université de Montréal (CRCHUM)CLSC Des Faubourgs, CIUSSS du Centre-Sud-de-L’Ile-de-MontréalDepartment of Microbiology, Infectious Diseases, and Immunology and Department of Pediatrics, Centre de Recherche du Centre Hospitalier, Université de Montréal, Universitaire Sainte-Justine (CHU Sainte-Justine)Department of Neurosciences, Université de Montréal and Centre de Recherche du CHUM (CRCHUM)Department of Neurosciences, Université de Montréal and Centre de Recherche du CHUM (CRCHUM)Department of Neurosciences, Université de Montréal and Centre de Recherche du CHUM (CRCHUM)Department of Neurosciences, Université de Montréal and Centre de Recherche du CHUM (CRCHUM)Department of Neurosciences, Université de Montréal and Centre de Recherche du CHUM (CRCHUM)Abstract Background Interleukin-27 (IL-27) can trigger both pro- and anti-inflammatory responses. This cytokine is elevated in the central nervous system (CNS) of multiple sclerosis (MS) patients, but how it influences neuroinflammatory processes remains unclear. As astrocytes express the receptor for IL-27, we sought to determine how these glial cells respond to this cytokine and whether such exposure alters their interactions with infiltrating activated T lymphocytes. To determine whether inflammation shapes the impact of IL-27, we compared the effects of this cytokine in non-inflamed and inflamed conditions induced by an IL-1β exposure. Main body Transcriptomic analysis of IL-27-exposed human astrocytes showed an upregulation of multiple immune genes. Human astrocytes increased the secretion of chemokines (CXCL9, CXCL10, and CXCL11) and the surface expression of proteins (PD-L1, HLA-E, and ICAM-1) following IL-27 exposure. To assess whether exposure of astrocytes to IL-27 influences the profile of activated T lymphocytes infiltrating the CNS, we used an astrocyte/T lymphocyte co-culture model. Activated human CD4+ or CD8+ T lymphocytes were co-cultured with astrocytes that have been either untreated or pre-exposed to IL‑27 or IL-1β. After 24 h, we analyzed T lymphocytes by flow cytometry for transcription factors and immune molecules. The contact with IL-27-exposed astrocytes increased the percentages of T-bet, Eomes, CD95, IL-18Rα, ICAM-1, and PD-L1 expressing CD4+ and CD8+ T lymphocytes and reduced the proportion of CXCR3-positive CD8+ T lymphocytes. Human CD8+ T lymphocytes co-cultured with human IL-27-treated astrocytes exhibited higher motility than when in contact with untreated astrocytes. These results suggested a preponderance of kinapse-like over synapse-like interactions between CD8+ T lymphocytes and IL-27-treated astrocytes. Finally, CD8+ T lymphocytes from MS patients showed higher motility in contact with IL-27-exposed astrocytes compared to healthy donors’ cells. Conclusion Our results establish that IL-27 alters the immune functions of human astrocytes and shapes the profile and motility of encountered T lymphocytes, especially CD8+ T lymphocytes from MS patients.https://doi.org/10.1186/s12974-022-02572-1CytokinesGlial cellsT lymphocytesTranscription factorsT cell motility |
| spellingShingle | Florent Lemaître Negar Farzam-kia Ana Carmena Moratalla Yves Carpentier Solorio Marie-Laure Clenet Olivier Tastet Aurélie Cleret-Buhot Jean Victor Guimond Elie Haddad Pierre Duquette J. Marc Girard Alexandre Prat Catherine Larochelle Nathalie Arbour IL-27 shapes the immune properties of human astrocytes and their impact on encountered human T lymphocytes Journal of Neuroinflammation Cytokines Glial cells T lymphocytes Transcription factors T cell motility |
| title | IL-27 shapes the immune properties of human astrocytes and their impact on encountered human T lymphocytes |
| title_full | IL-27 shapes the immune properties of human astrocytes and their impact on encountered human T lymphocytes |
| title_fullStr | IL-27 shapes the immune properties of human astrocytes and their impact on encountered human T lymphocytes |
| title_full_unstemmed | IL-27 shapes the immune properties of human astrocytes and their impact on encountered human T lymphocytes |
| title_short | IL-27 shapes the immune properties of human astrocytes and their impact on encountered human T lymphocytes |
| title_sort | il 27 shapes the immune properties of human astrocytes and their impact on encountered human t lymphocytes |
| topic | Cytokines Glial cells T lymphocytes Transcription factors T cell motility |
| url | https://doi.org/10.1186/s12974-022-02572-1 |
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