title: Microbial lipopeptides induce the production of IL-17 in Th cells.
abstract: Naive Th cells can be directed in vitro to develop into Th1 or Th2 cells by IL-12 or IL-4, respectively. In vivo, chronic immune reactions lead to polarized Th cytokine patterns. We found earlier that Borrelia burgdorferi, the spirochaete that causes Lyme disease, induces Th1 development in alpha beta TCR-transgenic Th cells. Here, we used TCR-transgenic Th cells and oligonucleotide arrays to analyze the differences between Th1 cells induced by IL-12 vs those induced by B. burgdorferi. Transgenic Th cells primed with peptide in the presence of B. burgdorferi expressed several mRNAs, including the mRNA encoding IL-17, at significantly higher levels than Th cells primed with peptide and IL-12. Cytometric single-cell analysis of Th cell cytokine production revealed that IL-17 cannot be categorized as either Th1 or Th2 cytokine. Instead, almost all IL-17-producing Th cells simultaneously produced TNF-alpha and most IL-17(+) Th cells also produced GM-CSF. This pattern was also observed in humans. Th cells from synovial fluid of patients with Lyme arthritis coexpressed IL-17 and TNF-alpha upon polyclonal stimulation. The induction of IL-17 production in Th cells is not restricted to B. burgdorferi. Priming of TCR-transgenic Th cells in the presence of mycobacterial lysates also induced IL-17/TNF-alpha coproduction. The physiological stimulus for IL-17 production was hitherto unknown. We show here for the first time that microbial stimuli induce the expression of IL-17 together with TNF-alpha in both murine and human T cells. Chronic IL-17 expression induced by microbes could be an important mediator of infection-induced immunopathology.
authors.affiliation: Deutsches Rheumaforschungszentrum, Berlin, Germany. Genetics Institute, Cambridge, MA 02140, USA.
authors.forename: C
authors.initials: C
authors.lastname: Infante-Duarte
authors.forename: H F
authors.initials: HF
authors.lastname: Horton
authors.forename: M C
authors.initials: MC
authors.lastname: Byrne
authors.forename: T
authors.initials: T
authors.lastname: Kamradt
mesh_terms: D000818:Animals; D016918:Arthritis, Reactive / Q000276:immunology; D001426:Bacterial Proteins / Q000138:chemical synthesis / Q000276:immunology*; D015748:Borrelia burgdorferi Group / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D016130:Immunophenotyping; D018664:Interleukin-12 / Q000502:physiology; D020381:Interleukin-17 / Q000096:biosynthesis*; D020382:Interleukin-18 / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D008074:Lipoproteins / Q000138:chemical synthesis / Q000276:immunology*; D008193:Lyme Disease / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; D018925:Chemokines; D016207:Cytokines; D020381:Interleukin-17; D020382:Interleukin-18; D015850:Interleukin-6; D008074:Lipoproteins; D010455:Peptides; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor