Induction of macrophage-derived chemokine/CCL22 expression in experimental autoimmune encephalomyelitis and cultured microglia: implications for disease regulation.
Macrophage-derived chemokine (MDC/CCL22) and its receptor CCR4 have been implicated in chronic inflammatory processes and in the homing of monocytes, Th2 cells and regulatory T-cell subsets. Here, we demonstrate that MDC and CCR4 mRNAs are expressed in the central nervous system (CNS) of mice developing relapsing-remitting and chronic-relapsing forms of experimental autoimmune encephalomyelitis (EAE). By immunohistochemistry, we show that MDC is produced by CNS-infiltrating leukocytes and intraparenchymal microglia, whereas CCR4 is expressed on some invading leukocytes. Upon in vitro activation, mouse microglia express MDC transcripts and secrete bioactive MDC that induces chemotaxis of Th2, but not Th1 cells. We suggest that MDC produced by microglia could regulate Th1-mediated CNS inflammation by facilitating the homing of Th2 and, possibly, regulatory T cells into the lesion site.
Columba-Cabezas
Sandra
S
Laboratory of Organ and System Pathophysiology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
Serafini
Barbara
B
Ambrosini
Elena
E
Sanchez
Massimo
M
Penna
Giuseppe
G
Adorini
Luciano
L
Aloisi
Francesca
F
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D054422:Chemokine CCL22; D019742:Chemokines, CC / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D007150:Immunohistochemistry; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D017628:Microglia / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D009103:Multiple Sclerosis / Q000276:immunology* / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
C515483:Ccl22 protein, mouse; C515355:Ccr4 protein, mouse; D054422:Chemokine CCL22; D019742:Chemokines, CC; D012333:RNA, Messenger; D054398:Receptors, CCR4; D019707:Receptors, Chemokine