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Blood, 2 April 2009, Vol. 113, No. 14, pp. 3190-3197. Prepublished online as a Blood First Edition Paper on February 5, 2009; DOI 10.1182/blood-2008-07-168575. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-07-168575v1 113/14/3190    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by King, I. L. Articles by Segal, B. M. Search for Related Content PubMed PubMed Citation Articles by King, I. L. Articles by Segal, B. M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 15, 2008 Accepted February 1, 2009 Circulating Ly-6C+ myeloid precursors migrate to the CNS and play a pathogenic role during autoimmune demyelinating disease Irah L. King, Travis L. Dickendesher, and Benjamin M. Segal* Interdepartmental Graduate Program in Neuroscience, School of Medicine and Dentistry, University of Rochester, Rochester, NY, United States Department of Neurology, Holtom-Garrett Program in Neuroimmunology, University of Michigan, Ann Arbor, MI, United States * Corresponding author; email: bmsegal{at}med.umich.edu. Mature myeloid cells (macrophages and CD11b+ dendritic cells) form a prominent component of neuroinflammatory infiltrates in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). The mechanism by which these cells are replenished during relapsing and chronic neuroinflammation is poorly understood. Here we demonstrate that CD11b+CD62L+Ly6Chi monocytes with colony forming potential are mobilized into the bloodstream by a GM-CSF dependent pathway immediately prior to EAE relapses. Circulating Ly6Chi monocytes traffic across the blood brain barrier (BBB), upregulate proinflammatory molecules and differentiate into CNS dendritic cells and macrophages. Enrichment of Ly6Chi monocytes in the circulating pool is associated with an earlier onset and increased severity of clinical EAE. Our studies indicate that GM-CSF driven release of Ly6Chi precursors from the bone marrow prevents exhaustion of CNS myeloid populations during relapsing or chronic autoimmune demyelination, suggesting a novel pathway for therapeutic targeting. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. J. E. Raveney, D. A. Copland, A. D. Dick, and L. B. Nicholson TNFR1-Dependent Regulation of Myeloid Cell Function in Experimental Autoimmune Uveoretinitis J. Immunol., August 15, 2009; 183(4): 2321 - 2329. [Abstract] [Full Text] [PDF]

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