Site-specific chemokine expression regulates central nervous system inflammation and determines clinical phenotype in autoimmune encephalomyelitis

• Published in: The Journal of immunology (1950) Vol. 193; no. 2; pp. 564 - 570
• Main Authors: Stoolman, Joshua S, Duncker, Patrick C, Huber, Amanda K, Segal, Benjamin M
• Format: Journal Article
• Language: English
• Published: United States 15-07-2014
• Subjects: Animals; Antigens, CD - immunology; Antigens, CD - metabolism; Antigens, Differentiation, T-Lymphocyte - immunology; Antigens, Differentiation, T-Lymphocyte - metabolism; Brain Stem - immunology; Brain Stem - metabolism; Brain Stem - pathology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Central Nervous System - immunology; Central Nervous System - metabolism; Central Nervous System - pathology; Chemokines - biosynthesis; Chemokines - immunology; Demyelinating Diseases - genetics; Demyelinating Diseases - immunology; Demyelinating Diseases - metabolism; Encephalomyelitis, Autoimmune, Experimental - genetics; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - metabolism; Flow Cytometry; Immunophenotyping; Inflammation - genetics; Inflammation - immunology; Inflammation - metabolism; Interferon gamma Receptor; Interleukin-12 - immunology; Interleukin-12 - metabolism; Interleukin-17 - immunology; Interleukin-17 - metabolism; Interleukin-2 Receptor alpha Subunit - immunology; Interleukin-2 Receptor alpha Subunit - metabolism; Lectins, C-Type - immunology; Lectins, C-Type - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Confocal; Monocytes - immunology; Monocytes - metabolism; Myelin-Oligodendrocyte Glycoprotein; Neutrophils - immunology; Neutrophils - metabolism; Peptide Fragments; Receptors, CCR2 - deficiency; Receptors, CCR2 - genetics; Receptors, CCR2 - immunology; Receptors, Interferon - deficiency; Receptors, Interferon - genetics; Receptors, Interferon - immunology; Receptors, Interleukin-8B - immunology; Receptors, Interleukin-8B - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1400825

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.