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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Chae, Wook-jin Solomon, Benjamin D. Bynoe, Margaret S. Mueller, Cynthia Alabanza, Leah M. |
| Description | Author Affiliation: Solomon BD ( Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.); |
| Abstract | Neuropilin-1 (Nrp1) is a cell surface molecule originally identified for its role in neuronal development. Recently, Nrp1 has been implicated in several aspects of immune function including maintenance of the immune synapse and development of regulatory T (T(reg)) cells. In this study, we provide evidence for a central role of Nrp1 in the regulation of CD4 T-cell immune responses in experimental autoimmune encephalitis (EAE). EAE serves as an animal model for the central nervous system (CNS) inflammatory disorder multiple sclerosis (MS). EAE is mediated primarily by CD4(+) T cells that migrate to the CNS and mount an inflammatory attack against myelin components, resulting in CNS pathology. Using a tissue-specific deletion system, we observed that the lack of Nrp1 on CD4(+) T cells results in increased EAE severity. These conditional knockout mice exhibit preferential T(H)-17 lineage commitment and decreased T(reg)-cell functionality. Conversely, CD4(+) T cells expressing Nrp1 suppress effector T-cell proliferation and cytokine production both in vivo and in vitro independent of T(reg) cells. Nrp1-mediated suppression can be inhibited by TGF-ß blockade but not by IL-10 blockade. These results suggest that Nrp1 is essential for proper maintenance of peripheral tolerance and its absence can result in unchecked autoreactive responses, leading to diseases like EAE and potentially MS. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 5 |
| Volume Number | 108 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2011-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | CD4-Positive T-Lymphocytes Immunology Encephalomyelitis, Autoimmune, Experimental Immunity, Cellular Neuropilin-1 Physiology Animals Interleukin-2 Receptor Alpha Subunit Mice Mice, Knockout Mice, Transgenic Genetics Research Support, N.I.H., Extramural Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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