The Th17–ELR+ CXC chemokine pathway is essential for the development of central nervous system autoimmune disease
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- Thaddeus Carlson
- 1Department of Microbiology and Immunology
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- Mark Kroenke
- 1Department of Microbiology and Immunology
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- Praveen Rao
- 1Department of Microbiology and Immunology
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- Thomas E. Lane
- 3Department of Molecular Biology and Biochemistry and Center for Immunology, University of California, Irvine, Irvine, CA 92697
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- Benjamin Segal
- 1Department of Microbiology and Immunology
書誌事項
- 公開日
- 2008-03-17
- DOI
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- 10.1084/jem.20072404
- 公開者
- Rockefeller University Press
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説明
<jats:p>The ELR+ CXC chemokines CXCL1 and CXCL2 are up-regulated in the central nervous system (CNS) during multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). However, their functional significance and the pathways regulating their expression are largely unknown. We show that transfer of encephalitogenic CD4+ Th17 cells is sufficient to induce CXCL1 and CXCL2 transcription in the spinal cords of naive, syngeneic recipients. Blockade or genetic silencing of CXCR2, a major receptor for these chemokines in mice, abrogates blood–brain barrier (BBB) breakdown, CNS infiltration by leukocytes, and the development of clinical deficits during the presentation as well as relapses of EAE. Depletion of circulating polymorphonuclear leukocytes (PMN) had a similar therapeutic effect. Furthermore, injection of CXCR2+ PMN into CXCR2−/− mice was sufficient to restore susceptibility to EAE. Our findings reveal that a Th17–ELR+ CXC chemokine pathway is critical for granulocyte mobilization, BBB compromise, and the clinical manifestation of autoimmune demyelination in myelin peptide–sensitized mice, and suggest new therapeutic targets for diseases such as MS.</jats:p>
収録刊行物
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- The Journal of Experimental Medicine
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The Journal of Experimental Medicine 205 (4), 811-823, 2008-03-17
Rockefeller University Press