Multiple sclerosis: cytokine receptors on oligodendrocytes predict innate regulation.
Multiple sclerosis (MS) is an immune-mediated demyelinating condition in which numerous soluble mediators have been implicated. We have extended the repertoire of cytokines studied in MS tissue by examining interleukin (IL-4), IL-6, IL-10, IL-12, IL-18, interferon (IFNgamma), and their receptors and have compared patterns with those seen in normal subjects and other neurological diseases (OND). Expression was evaluated by immunocytochemistry and Western blots. Remarkably, oligodendrocytes expressed all the cytokine receptors examined, particularly Th2-type, constitutively in normal subjects and upregulated in disease. Microglial cells also expressed cytokine receptors at similar levels. Cytokine expression was invariably a feature of microglial cells, except for IL-10, which was exclusively astrocytic. Oligodendrocytes did not display cytokines, except for low levels of IL-18. Although no pattern was specific for MS, most molecules were upregulated in MS and OND. Downstream JAK/STAT molecules were correspondingly upregulated. Cytokine receptors on oligodendrocytes (and microglia), and their corresponding ligands on microglia (and astrocytes), may implicate paracrine/autocrine regulation and may bespeak innate immunity in the central nervous system.
Cannella
Barbara
B
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. cannella@aecom.yu.edu
Raine
Cedric S
CS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000276:immunology* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053613:Janus Kinase 1; D008297:Male; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000276:immunology / Q000378:metabolism; D009836:Oligodendroglia / Q000276:immunology / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D018121:Receptors, Cytokine / Q000378:metabolism*; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000096:biosynthesis; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D018121:Receptors, Cytokine; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1