IFN-gamma regulates murine interferon-inducible T cell alpha chemokine (I-TAC) expression in dendritic cell lines and during experimental autoimmune encephalomyelitis (EAE).
Murine interferon-inducible T cell alpha chemokine (I-TAC) is a potent non-ELR Cys-X-Cys (CXC) chemokine that predominantly attracts activated T lymphocytes and binds to the receptor CXCR3. Using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) we analysed murine I-TAC expression in two different progenitor dendritic cell (DC) lines, MTHC-D2 and JAWS II which were exposed to various cytokines, and Con A-activated splenocytes from a panel of knockout mice. Analysis of the progenitor DC lines and Con A cultures demonstrated that murine I-TAC is primarily regulated by interferon (IFN)-gamma via interferon regulatory factor (IRF)-1. It has been proposed that I-TAC may have a role in autoimmune diseases such as multiple sclerosis (MS). Because I-TAC appears to be secreted from antigen-presenting cells (APCs) and attracts activated T cells, we examined the level of murine I-TAC mRNA in the central nervous system (CNS) of wild-type and IFN-gamma-receptor knockout (IFN-gammaR-/-) mice with myelin oligodendrocyte glycoprotein (MOG)35-55 peptide-induced experimental autoimmune encephalomyelitis (EAE). Peak I-TAC expression was detected in wild-type mice on day 14 when the mice begin to recover, whereas very low levels of I-TAC were detected in the CNS of IFN-gammaR-/- mice which develop severe EAE and die. The expression characteristics of murine I-TAC suggest an important mediator of immune cell communication that could augment vaccines and autoimmune therapies.
Hamilton
N H R
NH
John Curtin School of Medical Research (JCSMR), Australian National University, Canberra, Australian Capital Territory, Australia.
Banyer
J L
JL
Hapel
A J
AJ
Mahalingam
S
S
Ramsay
A J
AJ
Ramshaw
I A
IA
Thomson
S A
SA
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D019013:CD40 Antigens / Q000378:metabolism; D002460:Cell Line; D002490:Central Nervous System / Q000276:immunology; D054371:Chemokine CXCL11; D019743:Chemokines, CXC / Q000235:genetics*; D016207:Cytokines / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006023:Glycoproteins / Q000633:toxicity; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000633:toxicity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics; D000096743:Interferon gamma Receptor
D000906:Antibodies; D019013:CD40 Antigens; D054371:Chemokine CXCL11; D019743:Chemokines, CXC; D016207:Cytokines; D006023:Glycoproteins; D007371:Interferon-gamma; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D012333:RNA, Messenger; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C515203:Cxcl11 protein, mouse; C445081:myelin oligodendrocyte glycoprotein (35-55)