Interferon-γ/Interleukin-27 Axis Induces Programmed Death Ligand 1 Expression in Monocyte-Derived Dendritic Cells and Restores Immune Tolerance in Central Nervous System Autoimmunity
Antigen (Ag)-specific tolerance induction by intravenous (i. v.) injection of high-dose auto-Ags has been explored for therapy of autoimmune diseases, including multiple sclerosis (MS). It is thought that the advantage of such Ag-specific therapy over non-specific immunomodulatory treatments would b...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-10-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.576752/full |
| _version_ | 1819212628446150656 |
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| author | Giacomo Casella Javad Rasouli Rodolfo Thome Hélène C. Descamps Asrita Vattikonda Larissa Ishikawa Alexandra Boehm Daniel Hwang Weifeng Zhang Dan Xiao Jeongho Park Jeongho Park Guang-Xian Zhang Jorge I. Alvarez Abdolmohamad Rostami Bogoljub Ciric |
| author_facet | Giacomo Casella Javad Rasouli Rodolfo Thome Hélène C. Descamps Asrita Vattikonda Larissa Ishikawa Alexandra Boehm Daniel Hwang Weifeng Zhang Dan Xiao Jeongho Park Jeongho Park Guang-Xian Zhang Jorge I. Alvarez Abdolmohamad Rostami Bogoljub Ciric |
| author_sort | Giacomo Casella |
| collection | DOAJ |
| description | Antigen (Ag)-specific tolerance induction by intravenous (i. v.) injection of high-dose auto-Ags has been explored for therapy of autoimmune diseases, including multiple sclerosis (MS). It is thought that the advantage of such Ag-specific therapy over non-specific immunomodulatory treatments would be selective suppression of a pathogenic immune response without impairing systemic immunity, thus avoiding adverse effects of immunosuppression. Auto-Ag i.v. tolerance induction has been extensively studied in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and limited clinical trials demonstrated that it is safe and beneficial to a subset of MS patients. Nonetheless, the mechanisms of i.v. tolerance induction are incompletely understood, hampering the development of better approaches and their clinical application. Here, we describe a pathway whereby auto-Ag i.v. injected into mice with ongoing clinical EAE induces interferon-gamma (IFN-γ) secretion by auto-Ag-specific CD4+ T cells, triggering interleukin (IL)-27 production by conventional dendritic cells type 1 (cDC1). IL-27 then, via signal transducer and activator of transcription 3 activation, induces programmed death ligand 1 (PD-L1) expression by monocyte-derived dendritic cells (moDCs) in the central nervous system of mice with EAE. PD-L1 interaction with programmed cell death protein 1 on pathogenic CD4+ T cells leads to their apoptosis/anergy, resulting in disease amelioration. These findings identify a key role of the IFN-γ/IL-27/PD-L1 axis, involving T cells/cDC1/moDCs in the induction of i.v. tolerance. |
| first_indexed | 2024-12-23T06:45:59Z |
| format | Article |
| id | doaj.art-270b36e7c7d3452e82186e61202028fa |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-23T06:45:59Z |
| publishDate | 2020-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-270b36e7c7d3452e82186e61202028fa2022-12-21T17:56:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-10-011110.3389/fimmu.2020.576752576752Interferon-γ/Interleukin-27 Axis Induces Programmed Death Ligand 1 Expression in Monocyte-Derived Dendritic Cells and Restores Immune Tolerance in Central Nervous System AutoimmunityGiacomo Casella0Javad Rasouli1Rodolfo Thome2Hélène C. Descamps3Asrita Vattikonda4Larissa Ishikawa5Alexandra Boehm6Daniel Hwang7Weifeng Zhang8Dan Xiao9Jeongho Park10Jeongho Park11Guang-Xian Zhang12Jorge I. Alvarez13Abdolmohamad Rostami14Bogoljub Ciric15Department of Neurology, Thomas Jefferson University, Philadelphia, PA, United StatesDepartment of Neurology, Thomas Jefferson University, Philadelphia, PA, United StatesDepartment of Neurology, Thomas Jefferson University, Philadelphia, PA, United StatesDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesDepartment of Neurology, Thomas Jefferson University, Philadelphia, PA, United StatesDepartment of Neurology, Thomas Jefferson University, Philadelphia, PA, United StatesDepartment of Neurology, Thomas Jefferson University, Philadelphia, PA, United StatesDepartment of Neurology, Thomas Jefferson University, Philadelphia, PA, United StatesDepartment of Neurology, Thomas Jefferson University, Philadelphia, PA, United StatesDepartment of Neurology, Thomas Jefferson University, Philadelphia, PA, United StatesDepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United StatesCollege of Veterinary Medicine & Institute of Veterinary Science, Kangwon National University, Chuncheon, South KoreaDepartment of Neurology, Thomas Jefferson University, Philadelphia, PA, United StatesDepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United StatesDepartment of Neurology, Thomas Jefferson University, Philadelphia, PA, United StatesDepartment of Neurology, Thomas Jefferson University, Philadelphia, PA, United StatesAntigen (Ag)-specific tolerance induction by intravenous (i. v.) injection of high-dose auto-Ags has been explored for therapy of autoimmune diseases, including multiple sclerosis (MS). It is thought that the advantage of such Ag-specific therapy over non-specific immunomodulatory treatments would be selective suppression of a pathogenic immune response without impairing systemic immunity, thus avoiding adverse effects of immunosuppression. Auto-Ag i.v. tolerance induction has been extensively studied in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and limited clinical trials demonstrated that it is safe and beneficial to a subset of MS patients. Nonetheless, the mechanisms of i.v. tolerance induction are incompletely understood, hampering the development of better approaches and their clinical application. Here, we describe a pathway whereby auto-Ag i.v. injected into mice with ongoing clinical EAE induces interferon-gamma (IFN-γ) secretion by auto-Ag-specific CD4+ T cells, triggering interleukin (IL)-27 production by conventional dendritic cells type 1 (cDC1). IL-27 then, via signal transducer and activator of transcription 3 activation, induces programmed death ligand 1 (PD-L1) expression by monocyte-derived dendritic cells (moDCs) in the central nervous system of mice with EAE. PD-L1 interaction with programmed cell death protein 1 on pathogenic CD4+ T cells leads to their apoptosis/anergy, resulting in disease amelioration. These findings identify a key role of the IFN-γ/IL-27/PD-L1 axis, involving T cells/cDC1/moDCs in the induction of i.v. tolerance.https://www.frontiersin.org/articles/10.3389/fimmu.2020.576752/fullperipheral tolerancemonocytesexperimental autoimmune encephalitisPD-L1cytokines |
| spellingShingle | Giacomo Casella Javad Rasouli Rodolfo Thome Hélène C. Descamps Asrita Vattikonda Larissa Ishikawa Alexandra Boehm Daniel Hwang Weifeng Zhang Dan Xiao Jeongho Park Jeongho Park Guang-Xian Zhang Jorge I. Alvarez Abdolmohamad Rostami Bogoljub Ciric Interferon-γ/Interleukin-27 Axis Induces Programmed Death Ligand 1 Expression in Monocyte-Derived Dendritic Cells and Restores Immune Tolerance in Central Nervous System Autoimmunity Frontiers in Immunology peripheral tolerance monocytes experimental autoimmune encephalitis PD-L1 cytokines |
| title | Interferon-γ/Interleukin-27 Axis Induces Programmed Death Ligand 1 Expression in Monocyte-Derived Dendritic Cells and Restores Immune Tolerance in Central Nervous System Autoimmunity |
| title_full | Interferon-γ/Interleukin-27 Axis Induces Programmed Death Ligand 1 Expression in Monocyte-Derived Dendritic Cells and Restores Immune Tolerance in Central Nervous System Autoimmunity |
| title_fullStr | Interferon-γ/Interleukin-27 Axis Induces Programmed Death Ligand 1 Expression in Monocyte-Derived Dendritic Cells and Restores Immune Tolerance in Central Nervous System Autoimmunity |
| title_full_unstemmed | Interferon-γ/Interleukin-27 Axis Induces Programmed Death Ligand 1 Expression in Monocyte-Derived Dendritic Cells and Restores Immune Tolerance in Central Nervous System Autoimmunity |
| title_short | Interferon-γ/Interleukin-27 Axis Induces Programmed Death Ligand 1 Expression in Monocyte-Derived Dendritic Cells and Restores Immune Tolerance in Central Nervous System Autoimmunity |
| title_sort | interferon γ interleukin 27 axis induces programmed death ligand 1 expression in monocyte derived dendritic cells and restores immune tolerance in central nervous system autoimmunity |
| topic | peripheral tolerance monocytes experimental autoimmune encephalitis PD-L1 cytokines |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.576752/full |
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