PMID- 25005117 OWN - NLM STAT- MEDLINE DCOM- 20141111 LR - 20211021 IS - 1872-8421 (Electronic) IS - 0165-5728 (Print) IS - 0165-5728 (Linking) VI - 274 IP - 1-2 DP - 2014 Sep 15 TI - Astrocyte CCL2 sustains immune cell infiltration in chronic experimental autoimmune encephalomyelitis. PG - 53-61 LID - S0165-5728(14)00180-5 [pii] LID - 10.1016/j.jneuroim.2014.06.009 [doi] AB - Chemokine (C-C motif) ligand 2 (CCL2), initially identified as monocyte chemoattractant protein-1 (MCP-1), recruits immune cells to the central nervous system (CNS) during autoimmune inflammation. CCL2 can be expressed by multiple cell types, but which cells are responsible for CCL2 function during acute and chronic phases of autoimmune disease is not known. We determined the role of CCL2 in astrocytes in vivo during experimental autoimmune encephalomyelitis (EAE) by using Cre-loxP gene deletion. Mice with a conditional gene deletion of CCL2 from astrocytes had less severe EAE late in disease while having a similar incidence and severity of disease at onset as compared to wild type (WT) control littermates. EAE mice devoid of CCL2 in astrocytes had less macrophage and T cell inflammation in the white matter of the spinal cord and less diffuse activation of astrocytes and microglia in both white and gray matter as well as less axonal loss and demyelination, compared to WT littermates. These findings demonstrate that CCL2 in astrocytes plays an important role in the continued recruitment of immune cells and activation of glial cells in the CNS during chronic EAE, thereby suggesting a novel cell specific target for neuroprotective treatments of chronic neuroinflammatory diseases. CI - Copyright (c) 2014 Elsevier B.V. All rights reserved. FAU - Kim, Roy Y AU - Kim RY AD - Molecular Cellular and Integrative Physiology Interdepartmental Ph.D. Program, University of California, Los Angeles; Multiple Sclerosis Program, Department of Neurology, University of California, Los Angeles. FAU - Hoffman, Alexandria S AU - Hoffman AS AD - Multiple Sclerosis Program, Department of Neurology, University of California, Los Angeles. FAU - Itoh, Noriko AU - Itoh N AD - Multiple Sclerosis Program, Department of Neurology, University of California, Los Angeles. FAU - Ao, Yan AU - Ao Y AD - Department of Neurobiology, University of California, Los Angeles. FAU - Spence, Rory AU - Spence R AD - Multiple Sclerosis Program, Department of Neurology, University of California, Los Angeles. FAU - Sofroniew, Michael V AU - Sofroniew MV AD - Department of Neurobiology, University of California, Los Angeles. FAU - Voskuhl, Rhonda R AU - Voskuhl RR AD - Multiple Sclerosis Program, Department of Neurology, University of California, Los Angeles. Electronic address: rvoskuhl@ucla.edu. LA - eng GR - K24 NS062117/NS/NINDS NIH HHS/United States GR - T32 HD007228/HD/NICHD NIH HHS/United States GR - T32 HD07228-26/HD/NICHD NIH HHS/United States GR - K24NS052117/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20140624 PL - Netherlands TA - J Neuroimmunol JT - Journal of neuroimmunology JID - 8109498 RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) SB - IM MH - Animals MH - Astrocytes/*immunology MH - Chemokine CCL2/genetics/*immunology MH - Chronic Disease MH - Demyelinating Diseases/immunology MH - Encephalomyelitis, Autoimmune, Experimental/genetics/*immunology MH - Female MH - Macrophages/immunology MH - Male MH - Mice MH - Mice, Knockout MH - Microglia/immunology MH - Myelin Sheath/immunology MH - Spinal Cord/immunology MH - T-Lymphocytes/immunology PMC - PMC4343306 MID - NIHMS665299 OTO - NOTNLM OT - Astrocytes OT - CCL2 OT - EAE OT - Macrophage OT - Microglia OT - Multiple Sclerosis OT - Neuroprotection OT - T lymphocyte EDAT- 2014/07/10 06:00 MHDA- 2014/11/12 06:00 PMCR- 2015/02/27 CRDT- 2014/07/10 06:00 PHST- 2014/02/19 00:00 [received] PHST- 2014/06/09 00:00 [revised] PHST- 2014/06/17 00:00 [accepted] PHST- 2014/07/10 06:00 [entrez] PHST- 2014/07/10 06:00 [pubmed] PHST- 2014/11/12 06:00 [medline] PHST- 2015/02/27 00:00 [pmc-release] AID - S0165-5728(14)00180-5 [pii] AID - 10.1016/j.jneuroim.2014.06.009 [doi] PST - ppublish SO - J Neuroimmunol. 2014 Sep 15;274(1-2):53-61. doi: 10.1016/j.jneuroim.2014.06.009. Epub 2014 Jun 24.