The Innate Immune Receptor CD14 Mediates Lymphocyte Migration in EAE
Background: Multiple sclerosis is the most common autoimmune disease of the central nervous system in young adults and histopathologically characterized by inflammation, demyelination and gliosis. It is considered as a CD4+ T cell-mediated disease, but also a disease-promoting role of the innate imm...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2015-08-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | http://www.karger.com/Article/FullText/430351 |
| _version_ | 1818296993506656256 |
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| author | Ramona Halmer Laura Davies Yang Liu Klaus Fassbender Silke Walter |
| author_facet | Ramona Halmer Laura Davies Yang Liu Klaus Fassbender Silke Walter |
| author_sort | Ramona Halmer |
| collection | DOAJ |
| description | Background: Multiple sclerosis is the most common autoimmune disease of the central nervous system in young adults and histopathologically characterized by inflammation, demyelination and gliosis. It is considered as a CD4+ T cell-mediated disease, but also a disease-promoting role of the innate immune system has been proposed, based e.g. on the observation that innate immune receptors modulate disease severity of experimental autoimmune encephalomyelitis. Recent studies of our group provided first evidence for a key role of the innate immune LPS receptor (CD14) in pathophysiology of experimental autoimmune encephalomyelitis. CD14-deficient experimental autoimmune encephalomyelitis mice showed increased clinical symptoms and enhanced infiltration of monocytes and neutrophils in brain and spinal cord. Methods: In the current study, we further investigated the causes of the disease aggravation by CD14-deficiency and examined T cell activation, also focusing on the costimulatory molecules CTLA-4 and CD28, and T cell migration capacity over the blood brain barrier by FACS analysis, in vitro adhesion and transmigration assays. Results: In the results, we observed a significantly increased migration of CD14-deficient lymphocytes across an endothelial monolayer. In contrast, we did not see any differences in expression levels of TCR/CTLA-4 or TCR/CD28 and lymphocyte adhesion to endothelial cells from CD14-deficient compared to wildtype mice. Conclusion: The results demonstrate an important role of CD14 in migration of lymphocytes, and strengthen the importance of innate immune receptors in adaptive immune disorders, such as multiple sclerosis. |
| first_indexed | 2024-12-13T04:12:22Z |
| format | Article |
| id | doaj.art-10190d92d3fe4e71940498afe24e4d9b |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-13T04:12:22Z |
| publishDate | 2015-08-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-10190d92d3fe4e71940498afe24e4d9b2022-12-21T23:59:58ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-08-0137126927510.1159/000430351430351The Innate Immune Receptor CD14 Mediates Lymphocyte Migration in EAERamona HalmerLaura DaviesYang LiuKlaus FassbenderSilke WalterBackground: Multiple sclerosis is the most common autoimmune disease of the central nervous system in young adults and histopathologically characterized by inflammation, demyelination and gliosis. It is considered as a CD4+ T cell-mediated disease, but also a disease-promoting role of the innate immune system has been proposed, based e.g. on the observation that innate immune receptors modulate disease severity of experimental autoimmune encephalomyelitis. Recent studies of our group provided first evidence for a key role of the innate immune LPS receptor (CD14) in pathophysiology of experimental autoimmune encephalomyelitis. CD14-deficient experimental autoimmune encephalomyelitis mice showed increased clinical symptoms and enhanced infiltration of monocytes and neutrophils in brain and spinal cord. Methods: In the current study, we further investigated the causes of the disease aggravation by CD14-deficiency and examined T cell activation, also focusing on the costimulatory molecules CTLA-4 and CD28, and T cell migration capacity over the blood brain barrier by FACS analysis, in vitro adhesion and transmigration assays. Results: In the results, we observed a significantly increased migration of CD14-deficient lymphocytes across an endothelial monolayer. In contrast, we did not see any differences in expression levels of TCR/CTLA-4 or TCR/CD28 and lymphocyte adhesion to endothelial cells from CD14-deficient compared to wildtype mice. Conclusion: The results demonstrate an important role of CD14 in migration of lymphocytes, and strengthen the importance of innate immune receptors in adaptive immune disorders, such as multiple sclerosis.http://www.karger.com/Article/FullText/430351Multiple sclerosisExperimental autoimmune encephalomyelitisLPS receptorT cell activationBlood brain barrier |
| spellingShingle | Ramona Halmer Laura Davies Yang Liu Klaus Fassbender Silke Walter The Innate Immune Receptor CD14 Mediates Lymphocyte Migration in EAE Cellular Physiology and Biochemistry Multiple sclerosis Experimental autoimmune encephalomyelitis LPS receptor T cell activation Blood brain barrier |
| title | The Innate Immune Receptor CD14 Mediates Lymphocyte Migration in EAE |
| title_full | The Innate Immune Receptor CD14 Mediates Lymphocyte Migration in EAE |
| title_fullStr | The Innate Immune Receptor CD14 Mediates Lymphocyte Migration in EAE |
| title_full_unstemmed | The Innate Immune Receptor CD14 Mediates Lymphocyte Migration in EAE |
| title_short | The Innate Immune Receptor CD14 Mediates Lymphocyte Migration in EAE |
| title_sort | innate immune receptor cd14 mediates lymphocyte migration in eae |
| topic | Multiple sclerosis Experimental autoimmune encephalomyelitis LPS receptor T cell activation Blood brain barrier |
| url | http://www.karger.com/Article/FullText/430351 |
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