Lymphoid chemokines CCL19 and CCL21 are expressed in the central nervous system during experimental autoimmune encephalomyelitis: implications for the maintenance of chronic neuroinflammation.
The simultaneous presence of dendritic, T- and B-cells in the central nervous system (CNS) of mice with experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis, suggests that interactions among these cell types might be instrumental in the local induction and maintenance of autoimmune reactions. In this study, we explored the possibility that such aberrant leukocyte recruitment in the CNS could be sustained by "lymphoid" chemokines which orchestrate dendritic cell and lymphocyte homing to lymphoid organs. Transcripts for CCL19 and CCL21 and their common receptor CCR7 were induced in the CNS of mice undergoing relapsing-remitting and chronic-relapsing EAE. While CCL21 immunoreactivity was confined to the endothelium of some inflamed blood vessels, CCL19 was expressed by many infiltrating leukocytes and some astrocytes and microglia in the CNS parenchyma. CCR7+ cells accumulated in inflammatory lesions during EAE progression, when abundant infiltration of the CNS by mature dendritic cells, B-cells and cells expressing naive T-cell markers also occurred. These findings suggest that CCL19 and CCL21 produced in the EAE-affected CNS may be critical for the homing of antigen presenting cells and lymphocytes, resulting in continuous local antigenic stimulation and maintenance of chronic neuroinflammation.
Columba-Cabezas
Sandra
S
Laboratory of Organ and System Pathophysiology, Istituto Superiore di Sanità, Roma, Italy.
Serafini
Barbara
B
Ambrosini
Elena
E
Aloisi
Francesca
F
D000818:Animals; D001253:Astrocytes / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001921:Brain / Q000276:immunology / Q000473:pathology; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology*; D005260:Female; D007150:Immunohistochemistry; D017628:Microglia / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC; D012333:RNA, Messenger; D054400:Receptors, CCR7; D019707:Receptors, Chemokine