Antoine Philippe Fournier, Stephanie Zandee, Marc Charabati, Evelyn Peelen, Olivier Tastet, Jorge Ivan Alvarez, Hania Kebir, Lyne Bourbonnière, Sandra Larouche, Boaz Lahav, Wendy Klement, Fiona Tea, Alain Bouthillier, Robert Moumdjian, Romain Cayrol, Pierre Duquette, Marc Girard, Catherine Larochelle, Nathalie Arbour, Alexandre Prat
{"title":"CLMP促进多发性硬化症患者白细胞跨脑屏障迁移。","authors":"Antoine Philippe Fournier, Stephanie Zandee, Marc Charabati, Evelyn Peelen, Olivier Tastet, Jorge Ivan Alvarez, Hania Kebir, Lyne Bourbonnière, Sandra Larouche, Boaz Lahav, Wendy Klement, Fiona Tea, Alain Bouthillier, Robert Moumdjian, Romain Cayrol, Pierre Duquette, Marc Girard, Catherine Larochelle, Nathalie Arbour, Alexandre Prat","doi":"10.1212/NXI.0000000000200022","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objectives: </strong>In multiple sclerosis (MS), peripheral immune cells use various cell trafficking molecules to infiltrate the CNS where they cause damage.The objective of this study was to investigate the involvement of coxsackie and adenovirus receptor-like membrane protein (CLMP) in the migration of immune cells into the CNS of patients with MS.</p><p><strong>Methods: </strong>Expression of CLMP was measured in primary cultures of human brain endothelial cells (HBECs) and human meningeal endothelial cells (HMECs), postmortem brain samples, and peripheral blood mononuclear cells (PBMCs) from patients with MS and controls by RNA sequencing, quantitative PCR, immunohistochemistry, and flow cytometry. In vitro migration assays using HBECs and HMECs were performed to evaluate the function of CLMP.</p><p><strong>Results: </strong>Using bulk RNA sequencing of primary cultures of human brain and meningeal endothelial cells (ECs), we have identified CLMP as a new potential cell trafficking molecule upregulated in inflammatory conditions. We first confirmed the upregulation of CLMP at the protein level on TNFα-activated and IFNγ-activated primary cultures of human brain and meningeal ECs. In autopsy brain specimens from patients with MS, we demonstrated an overexpression of endothelial CLMP in active MS lesions when compared with normal control brain tissue. Flow cytometry of human PBMCs demonstrated an increased frequency of CLMP<sup>+</sup> B lymphocytes and monocytes in patients with MS, when compared with that in healthy controls. The use of a blocking antibody against CLMP reduced the migration of immune cells across the human brain and meningeal ECs in vitro. Finally, we found CLMP<sup>+</sup> immune cell infiltrates in the perivascular area of parenchymal lesions and in the meninges of patients with MS.</p><p><strong>Discussion: </strong>Collectively, our data demonstrate that CLMP is an adhesion molecule used by immune cells to access the CNS during neuroinflammatory disorders such as MS. CLMP could represent a target for a new treatment of neuroinflammatory conditions.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":7.5000,"publicationDate":"2022-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7b/f7/NXI-2022-200028.PMC9465835.pdf","citationCount":"3","resultStr":"{\"title\":\"CLMP Promotes Leukocyte Migration Across Brain Barriers in Multiple Sclerosis.\",\"authors\":\"Antoine Philippe Fournier, Stephanie Zandee, Marc Charabati, Evelyn Peelen, Olivier Tastet, Jorge Ivan Alvarez, Hania Kebir, Lyne Bourbonnière, Sandra Larouche, Boaz Lahav, Wendy Klement, Fiona Tea, Alain Bouthillier, Robert Moumdjian, Romain Cayrol, Pierre Duquette, Marc Girard, Catherine Larochelle, Nathalie Arbour, Alexandre Prat\",\"doi\":\"10.1212/NXI.0000000000200022\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objectives: </strong>In multiple sclerosis (MS), peripheral immune cells use various cell trafficking molecules to infiltrate the CNS where they cause damage.The objective of this study was to investigate the involvement of coxsackie and adenovirus receptor-like membrane protein (CLMP) in the migration of immune cells into the CNS of patients with MS.</p><p><strong>Methods: </strong>Expression of CLMP was measured in primary cultures of human brain endothelial cells (HBECs) and human meningeal endothelial cells (HMECs), postmortem brain samples, and peripheral blood mononuclear cells (PBMCs) from patients with MS and controls by RNA sequencing, quantitative PCR, immunohistochemistry, and flow cytometry. In vitro migration assays using HBECs and HMECs were performed to evaluate the function of CLMP.</p><p><strong>Results: </strong>Using bulk RNA sequencing of primary cultures of human brain and meningeal endothelial cells (ECs), we have identified CLMP as a new potential cell trafficking molecule upregulated in inflammatory conditions. We first confirmed the upregulation of CLMP at the protein level on TNFα-activated and IFNγ-activated primary cultures of human brain and meningeal ECs. In autopsy brain specimens from patients with MS, we demonstrated an overexpression of endothelial CLMP in active MS lesions when compared with normal control brain tissue. Flow cytometry of human PBMCs demonstrated an increased frequency of CLMP<sup>+</sup> B lymphocytes and monocytes in patients with MS, when compared with that in healthy controls. The use of a blocking antibody against CLMP reduced the migration of immune cells across the human brain and meningeal ECs in vitro. Finally, we found CLMP<sup>+</sup> immune cell infiltrates in the perivascular area of parenchymal lesions and in the meninges of patients with MS.</p><p><strong>Discussion: </strong>Collectively, our data demonstrate that CLMP is an adhesion molecule used by immune cells to access the CNS during neuroinflammatory disorders such as MS. CLMP could represent a target for a new treatment of neuroinflammatory conditions.</p>\",\"PeriodicalId\":520720,\"journal\":{\"name\":\"Neurology(R) neuroimmunology & neuroinflammation\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":7.5000,\"publicationDate\":\"2022-09-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7b/f7/NXI-2022-200028.PMC9465835.pdf\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurology(R) neuroimmunology & neuroinflammation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1212/NXI.0000000000200022\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/11/1 0:00:00\",\"PubModel\":\"Print\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurology(R) neuroimmunology & neuroinflammation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1212/NXI.0000000000200022","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/11/1 0:00:00","PubModel":"Print","JCR":"","JCRName":"","Score":null,"Total":0}
CLMP Promotes Leukocyte Migration Across Brain Barriers in Multiple Sclerosis.
Background and objectives: In multiple sclerosis (MS), peripheral immune cells use various cell trafficking molecules to infiltrate the CNS where they cause damage.The objective of this study was to investigate the involvement of coxsackie and adenovirus receptor-like membrane protein (CLMP) in the migration of immune cells into the CNS of patients with MS.
Methods: Expression of CLMP was measured in primary cultures of human brain endothelial cells (HBECs) and human meningeal endothelial cells (HMECs), postmortem brain samples, and peripheral blood mononuclear cells (PBMCs) from patients with MS and controls by RNA sequencing, quantitative PCR, immunohistochemistry, and flow cytometry. In vitro migration assays using HBECs and HMECs were performed to evaluate the function of CLMP.
Results: Using bulk RNA sequencing of primary cultures of human brain and meningeal endothelial cells (ECs), we have identified CLMP as a new potential cell trafficking molecule upregulated in inflammatory conditions. We first confirmed the upregulation of CLMP at the protein level on TNFα-activated and IFNγ-activated primary cultures of human brain and meningeal ECs. In autopsy brain specimens from patients with MS, we demonstrated an overexpression of endothelial CLMP in active MS lesions when compared with normal control brain tissue. Flow cytometry of human PBMCs demonstrated an increased frequency of CLMP+ B lymphocytes and monocytes in patients with MS, when compared with that in healthy controls. The use of a blocking antibody against CLMP reduced the migration of immune cells across the human brain and meningeal ECs in vitro. Finally, we found CLMP+ immune cell infiltrates in the perivascular area of parenchymal lesions and in the meninges of patients with MS.
Discussion: Collectively, our data demonstrate that CLMP is an adhesion molecule used by immune cells to access the CNS during neuroinflammatory disorders such as MS. CLMP could represent a target for a new treatment of neuroinflammatory conditions.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
