title: Galectin-3 modulates Th17 responses by regulating dendritic cell cytokines.
abstract: Galectin-3 is a β-galactoside-binding animal lectin with diverse functions, including regulation of T helper (Th) 1 and Th2 responses. Current data indicate that galectin-3 expressed in dendritic cells (DCs) may be contributory. Th17 cells have emerged as critical inducers of tissue inflammation in autoimmune disease and important mediators of host defense against fungal pathogens, although little is known about galectin-3 involvement in Th17 development. We investigated the role of galectin-3 in the induction of Th17 immunity in galectin-3-deficient (gal3(-/-)) and gal3(+/+) mouse bone marrow-derived DCs. We demonstrate that intracellular galectin-3 negatively regulates Th17 polarization in response to the dectin-1 agonist curdlan (a β-glucan present on the cell wall of fungal species) and lipopolysaccharide, agents that prime DCs for Th17 differentiation. On activation of dectin-1, gal3(-/-) DCs secreted higher levels of the Th17-axis cytokine IL-23 compared with gal3(+/+) DCs and contained higher levels of activated c-Rel, an NF-κB subunit that promotes IL-23 expression. Levels of active Raf-1, a kinase that participates in downstream inhibition of c-Rel binding to the IL23A promoter, were impaired in gal3(-/-) DCs. Modulation of Th17 by galectin-3 in DCs also occurred in vivo because adoptive transfer of gal3(-/-) DCs exposed to Candida albicans conferred higher Th17 responses and protection against fungal infection. We conclude that galectin-3 suppresses Th17 responses by regulating DC cytokine production.
authors.affiliation: Department of Dermatology, University of California, Davis, School of Medicine, Sacramento, California.
authors.forename: Agnes
authors.initials: A
authors.lastname: Fermin Lee
authors.affiliation: Department of Dermatology, University of California, Davis, School of Medicine, Sacramento, California; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Huan-Yuan
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Lei
authors.initials: L
authors.lastname: Wan
authors.affiliation: Graduate Institute of Immunology, National Taiwan University, College of Medicine, Taipei, Taiwan.
authors.forename: Sheng-Yang
authors.initials: SY
authors.lastname: Wu
authors.affiliation: Graduate Institute of Immunology, National Taiwan University, College of Medicine, Taipei, Taiwan.
authors.forename: Jhang-Sian
authors.initials: JS
authors.lastname: Yu
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Annie C
authors.initials: AC
authors.lastname: Huang
authors.affiliation: Graduate Institute of Immunology, National Taiwan University, College of Medicine, Taipei, Taiwan.
authors.forename: Shi-Chuen
authors.initials: SC
authors.lastname: Miaw
authors.affiliation: Department of Dermatology, University of California, Davis, School of Medicine, Sacramento, California; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Immunology, National Taiwan University, College of Medicine, Taipei, Taiwan.
authors.forename: Betty A
authors.initials: BA
authors.lastname: Wu-Hsieh
authors.affiliation: Department of Dermatology, University of California, Davis, School of Medicine, Sacramento, California; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Electronic address: fliu@ucdavis.edu.
authors.forename: Fu-Tong
authors.initials: FT
authors.lastname: Liu
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002176:Candida albicans / Q000276:immunology / Q000502:physiology; D002177:Candidiasis / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016764:Cell Polarity / Q000187:drug effects; D002645:Chickens; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000382:microbiology; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D037502:Galectin 3 / Q000172:deficiency / Q000378:metabolism*; D007109:Immunity / Q000187:drug effects; D053759:Interleukin-23 / Q000096:biosynthesis; D037181:Lectins, C-Type / Q000819:agonists; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D020569:Proto-Oncogene Proteins c-rel / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology*; D047071:beta-Glucans / Q000494:pharmacology; D000099181:Dectin-1
chemical_list: D016207:Cytokines; D048049:Extracellular Signal-Regulated MAP Kinases; D037502:Galectin 3; D053759:Interleukin-23; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D019908:Proto-Oncogene Proteins c-raf; D020569:Proto-Oncogene Proteins c-rel; D047071:beta-Glucans; D000099181:Dectin-1; C038459:curdlan
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