title: The encephalitogenicity of T(H)17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF.
abstract: Interleukin 17 (IL-17)-producing helper T cells (T(H)17 cells) require exposure to IL-23 to become encephalitogenic, but the mechanism by which IL-23 promotes their pathogenicity is not known. Here we found that IL-23 induced production of the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) in T(H)17 cells and that GM-CSF had an essential role in their encephalitogenicity. Our findings identify a chief mechanism that underlies the important role of IL-23 in autoimmune diseases. IL-23 induced a positive feedback loop whereby GM-CSF secreted by T(H)17 cells stimulated the production of IL-23 by antigen-presenting cells. Such cross-regulation of IL-23 and GM-CSF explains the similar pattern of resistance to autoimmunity when either of the two cytokines is absent and identifies T(H)17 cells as a crucial source of GM-CSF in autoimmune inflammation.
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Mohamed
authors.initials: M
authors.lastname: El-Behi
authors.forename: Bogoljub
authors.initials: B
authors.lastname: Ciric
authors.forename: Hong
authors.initials: H
authors.lastname: Dai
authors.forename: Yaping
authors.initials: Y
authors.lastname: Yan
authors.forename: Melissa
authors.initials: M
authors.lastname: Cullimore
authors.forename: Farinaz
authors.initials: F
authors.lastname: Safavi
authors.forename: Guang-Xian
authors.initials: GX
authors.lastname: Zhang
authors.forename: Bonnie N
authors.initials: BN
authors.lastname: Dittel
authors.forename: Abdolmohamad
authors.initials: A
authors.lastname: Rostami
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D039521:CD11c Antigen / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000494:pharmacology; D053759:Interleukin-23 / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D063308:Myelin-Oligodendrocyte Glycoprotein; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D000906:Antibodies; D039521:CD11c Antigen; D006023:Glycoproteins; D007375:Interleukin-1; D053583:Interleukin-1beta; D053759:Interleukin-23; D063308:Myelin-Oligodendrocyte Glycoprotein; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D010446:Peptide Fragments; D016212:Transforming Growth Factor beta; C445081:myelin oligodendrocyte glycoprotein (35-55); D016178:Granulocyte-Macrophage Colony-Stimulating Factor