Single-cell mass cytometry on peripheral cells in Myasthenia Gravis identifies dysregulation of innate immune cells
Myasthenia Gravis (MG) is a neurological autoimmune disease characterized by disabling muscle weaknesses due to anti-acetylcholine receptor (AChR) autoantibodies. To gain insight into immune dysregulation underlying early-onset AChR+ MG, we performed an in-depth analysis of peripheral mononuclear bl...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1083218/full |
| _version_ | 1828051370899406848 |
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| author | Julien Verdier Odessa-Maud Fayet Edouard Hemery Frédérique Truffault Natalia Pinzón Sophie Demeret Anthony Behin Elie Fadel Julien Guihaire Aurélien Corneau Catherine Blanc Sonia Berrih-Aknin Rozen Le Panse |
| author_facet | Julien Verdier Odessa-Maud Fayet Edouard Hemery Frédérique Truffault Natalia Pinzón Sophie Demeret Anthony Behin Elie Fadel Julien Guihaire Aurélien Corneau Catherine Blanc Sonia Berrih-Aknin Rozen Le Panse |
| author_sort | Julien Verdier |
| collection | DOAJ |
| description | Myasthenia Gravis (MG) is a neurological autoimmune disease characterized by disabling muscle weaknesses due to anti-acetylcholine receptor (AChR) autoantibodies. To gain insight into immune dysregulation underlying early-onset AChR+ MG, we performed an in-depth analysis of peripheral mononuclear blood cells (PBMCs) using mass cytometry. PBMCs from 24 AChR+ MG patients without thymoma and 16 controls were stained with a panel of 37 antibodies. Using both unsupervised and supervised approaches, we observed a decrease in monocytes, for all subpopulations: classical, intermediate, and non-classical monocytes. In contrast, an increase in innate lymphoid cells 2 (ILC2s) and CD27- γδ T cells was observed. We further investigated the dysregulations affecting monocytes and γδ T cells in MG. We analyzed CD27- γδ T cells in PBMCs and thymic cells from AChR+ MG patients. We detected the increase in CD27- γδ T cells in thymic cells of MG patients suggesting that the inflammatory thymic environment might affect γδ T cell differentiation. To better understand changes that might affect monocytes, we analyzed RNA sequencing data from CD14+ PBMCs and showed a global decrease activity of monocytes in MG patients. Next, by flow cytometry, we especially confirmed the decrease affecting non-classical monocytes. In MG, as for other B-cell mediated autoimmune diseases, dysregulations are well known for adaptive immune cells, such as B and T cells. Here, using single-cell mass cytometry, we unraveled unexpected dysregulations for innate immune cells. If these cells are known to be crucial for host defense, our results demonstrated that they could also be involved in autoimmunity. |
| first_indexed | 2024-04-10T19:36:41Z |
| format | Article |
| id | doaj.art-7eac36fa8244491c8d5bd94c66c0d637 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T19:36:41Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-7eac36fa8244491c8d5bd94c66c0d6372023-01-30T05:02:56ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-01-011410.3389/fimmu.2023.10832181083218Single-cell mass cytometry on peripheral cells in Myasthenia Gravis identifies dysregulation of innate immune cellsJulien Verdier0Odessa-Maud Fayet1Edouard Hemery2Frédérique Truffault3Natalia Pinzón4Sophie Demeret5Anthony Behin6Elie Fadel7Julien Guihaire8Aurélien Corneau9Catherine Blanc10Sonia Berrih-Aknin11Rozen Le Panse12Sorbonne University, INSERM, Institute of Myology, Center of Research in Myology, Paris, FranceSorbonne University, INSERM, Institute of Myology, Center of Research in Myology, Paris, FranceSorbonne University, INSERM, Institute of Myology, Center of Research in Myology, Paris, FranceSorbonne University, INSERM, Institute of Myology, Center of Research in Myology, Paris, FranceSorbonne University, INSERM, Institute of Myology, Center of Research in Myology, Paris, FranceAPHP, Assistance Publique - Hopitaux de Paris, Paris, FranceAP-HP, Referral Center for Neuromuscular Disorders, Institute of Myology, Pitié-Salpêtrière Hospital, Paris, FranceMarie Lannelongue Hospital, Paris-Sud University, Le Plessis-Robinson, FranceMarie Lannelongue Hospital, Paris-Sud University, Le Plessis-Robinson, FrancePlateforme de Cytométrie de la Pitié-Salpétrière (CyPS), UMS037-PASS, Sorbonne Université-Faculté de Médecine, Paris, FrancePlateforme de Cytométrie de la Pitié-Salpétrière (CyPS), UMS037-PASS, Sorbonne Université-Faculté de Médecine, Paris, FranceSorbonne University, INSERM, Institute of Myology, Center of Research in Myology, Paris, FranceSorbonne University, INSERM, Institute of Myology, Center of Research in Myology, Paris, FranceMyasthenia Gravis (MG) is a neurological autoimmune disease characterized by disabling muscle weaknesses due to anti-acetylcholine receptor (AChR) autoantibodies. To gain insight into immune dysregulation underlying early-onset AChR+ MG, we performed an in-depth analysis of peripheral mononuclear blood cells (PBMCs) using mass cytometry. PBMCs from 24 AChR+ MG patients without thymoma and 16 controls were stained with a panel of 37 antibodies. Using both unsupervised and supervised approaches, we observed a decrease in monocytes, for all subpopulations: classical, intermediate, and non-classical monocytes. In contrast, an increase in innate lymphoid cells 2 (ILC2s) and CD27- γδ T cells was observed. We further investigated the dysregulations affecting monocytes and γδ T cells in MG. We analyzed CD27- γδ T cells in PBMCs and thymic cells from AChR+ MG patients. We detected the increase in CD27- γδ T cells in thymic cells of MG patients suggesting that the inflammatory thymic environment might affect γδ T cell differentiation. To better understand changes that might affect monocytes, we analyzed RNA sequencing data from CD14+ PBMCs and showed a global decrease activity of monocytes in MG patients. Next, by flow cytometry, we especially confirmed the decrease affecting non-classical monocytes. In MG, as for other B-cell mediated autoimmune diseases, dysregulations are well known for adaptive immune cells, such as B and T cells. Here, using single-cell mass cytometry, we unraveled unexpected dysregulations for innate immune cells. If these cells are known to be crucial for host defense, our results demonstrated that they could also be involved in autoimmunity.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1083218/fullautoimmunityCyTOF mass cytometrymonocytesγδ T cellsinnate lymphoid cellsthymus |
| spellingShingle | Julien Verdier Odessa-Maud Fayet Edouard Hemery Frédérique Truffault Natalia Pinzón Sophie Demeret Anthony Behin Elie Fadel Julien Guihaire Aurélien Corneau Catherine Blanc Sonia Berrih-Aknin Rozen Le Panse Single-cell mass cytometry on peripheral cells in Myasthenia Gravis identifies dysregulation of innate immune cells Frontiers in Immunology autoimmunity CyTOF mass cytometry monocytes γδ T cells innate lymphoid cells thymus |
| title | Single-cell mass cytometry on peripheral cells in Myasthenia Gravis identifies dysregulation of innate immune cells |
| title_full | Single-cell mass cytometry on peripheral cells in Myasthenia Gravis identifies dysregulation of innate immune cells |
| title_fullStr | Single-cell mass cytometry on peripheral cells in Myasthenia Gravis identifies dysregulation of innate immune cells |
| title_full_unstemmed | Single-cell mass cytometry on peripheral cells in Myasthenia Gravis identifies dysregulation of innate immune cells |
| title_short | Single-cell mass cytometry on peripheral cells in Myasthenia Gravis identifies dysregulation of innate immune cells |
| title_sort | single cell mass cytometry on peripheral cells in myasthenia gravis identifies dysregulation of innate immune cells |
| topic | autoimmunity CyTOF mass cytometry monocytes γδ T cells innate lymphoid cells thymus |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1083218/full |
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