Induction of the genes for Cxcl9 and Cxcl10 is dependent on IFN-gamma but shows differential cellular expression in experimental autoimmune encephalomyelitis and by astrocytes and microglia in vitro.
The chemokines CXCL9 and CXCL10 bind to the common receptor CXCR3 and are implicated in the pathogenesis of T-cell-mediated immunity in the central nervous system (CNS). Here we examined the temporal and spatial regulation of the Cxcl9 and Cxcl10 genes in the CNS of mice with myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) and by glial cells in vitro. During peak disease the levels of CXCL9 and CXCL10 mRNA and protein were increased significantly in the cerebellum and spinal cord but were reduced during the recovery phase. Expression of these genes in the CNS was abolished in IFN-gamma-receptor deficient mice with MOG-EAE. In wild-type mice, CXCL9 RNA was localized mainly to infiltrating mononuclear cells including lesion and perilesional microglia, while CXCL10 RNA was seen primarily in more distal astrocytes that surrounded the inflammatory lesions. Examination of cultured glia following treatment with IFN-gamma revealed that while both CXCL9 and CXCL10 mRNA transcripts were induced in microglia, only CXCL10 mRNA was induced in astrocytes. Thus, although IFN-gamma is the pivotal mediator of both Cxcl10 and Cxcl9 gene expression in EAE, this cytokine differentially regulates the expression of these genes by astrocytes and microglia. The differential glial localization of these chemokines in EAE suggests CXCL9 and CXCL10 have specialized functions.
Carter
Sally L
SL
School of Molecular and Microbial Biosciences, The University of Sydney, NSW, Australia.
Müller
Marcus
M
Manders
Peter M
PM
Campbell
Iain L
IL
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000096:biosynthesis / Q000235:genetics*; D054370:Chemokine CXCL9 / Q000096:biosynthesis / Q000235:genetics*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017471:Receptors, Interferon / Q000172:deficiency; D014018:Tissue Distribution; D000096743:Interferon gamma Receptor
D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D007371:Interferon-gamma; D012333:RNA, Messenger; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor