title: Site-specific chemokine expression regulates central nervous system inflammation and determines clinical phenotype in autoimmune encephalomyelitis.
abstract: The adoptive transfer of myelin-reactive T cells into wild-type hosts results in spinal cord inflammation and ascending paralysis, referred to as conventional experimental autoimmune encephalomyelitis (EAE), as opposed to brainstem inflammation and ataxia, which characterize disease in IFN-γRKO hosts (atypical EAE). In this article, we show that atypical EAE correlates with preferential upregulation of CXCL2 in the brainstem, and is driven by CXCR2-dependent recruitment of neutrophils. In contrast, conventional EAE is associated with upregulation of CCL2 in the spinal cord, and is driven by recruitment of monocytes via a partially CCR2-dependent pathway. This study illustrates how regional differences in chemokine expression within a target organ shape the spatial pattern and composition of autoimmune infiltrates, leading to disparate clinical outcomes.
authors.affiliation: Department of Neurology, Holtom-Garrett Program in Neuroimmunology and Multiple Sclerosis Center, University of Michigan School of Medicine, Ann Arbor, MI 48109; Graduate Program in Immunology, University of Michigan School of Medicine, Ann Arbor, MI 48109; and.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Stoolman
authors.affiliation: Department of Neurology, Holtom-Garrett Program in Neuroimmunology and Multiple Sclerosis Center, University of Michigan School of Medicine, Ann Arbor, MI 48109; Graduate Program in Immunology, University of Michigan School of Medicine, Ann Arbor, MI 48109; and.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Duncker
authors.affiliation: Department of Neurology, Holtom-Garrett Program in Neuroimmunology and Multiple Sclerosis Center, University of Michigan School of Medicine, Ann Arbor, MI 48109;
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Huber
authors.affiliation: Department of Neurology, Holtom-Garrett Program in Neuroimmunology and Multiple Sclerosis Center, University of Michigan School of Medicine, Ann Arbor, MI 48109; Graduate Program in Immunology, University of Michigan School of Medicine, Ann Arbor, MI 48109; and Neuroscience Program, University of Michigan School of Medicine, Ann Arbor, MI 48109 bmsegal@umich.edu.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Segal
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D001933:Brain Stem / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002490:Central Nervous System / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018925:Chemokines / Q000096:biosynthesis / Q000276:immunology*; D003711:Demyelinating Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D016130:Immunophenotyping; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments; D054390:Receptors, CCR2 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D023063:Receptors, Interleukin-8B / Q000276:immunology / Q000378:metabolism; D000096743:Interferon gamma Receptor; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018925:Chemokines; D018664:Interleukin-12; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D054390:Receptors, CCR2; D017471:Receptors, Interferon; D023063:Receptors, Interleukin-8B; D000096743:Interferon gamma Receptor; D000099192:CD69 Antigens; C515335:Ccr2 protein, mouse; C445081:myelin oligodendrocyte glycoprotein (35-55)