title: Galectin-3 negatively regulates dendritic cell production of IL-23/IL-17-axis cytokines in infection by Histoplasma capsulatum.
abstract: Galectin-3 (gal3) is known for its immunoregulatory functions in infectious, autoimmune, and inflammatory diseases. However, little is known about its regulatory role in the host's IL-17A response to infection. Using a mouse model of histoplasmosis in which both Th1 and Th17 responses contribute to fungal clearance, we investigated how gal3 regulates IL-17A responses. Our study showed that Histoplasma infection induced gal3(-/-) dendritic cells to produce significantly higher levels of IL-23, TGF-β1, and IL-1β than did gal3(+/+) cells. Infected by the same inoculum of Histoplasma, gal3(-/-) mice had lower fungal burden and produced higher levels of IL-23/IL-17-axis cytokines and lower levels of IL-12 and IFN-γ. Additionally, there was an increase in Th17 cells and a reduction in Th1 cells in infected gal3(-/-) mice. In vitro Th1/Th17-skewing experiments excluded the intrinsic effect of gal3 on Th cell differentiation. Although neutrophils from both gal3(+/+) and gal3(-/-) mice produced IL-17A upon IL-23 stimulation, their contribution to IL-17A production was greater in gal3(-/-) mice than in gal3(+/+) mice. Compared with gal3(+/+) dendritic cells, adoptive transfer of gal3(-/-) dendritic cells resulted in production of significantly higher levels of IL-17-axis cytokines and reduced fungal burden. It appears that reduced fungal burden and preferential IL-17A response in gal3(-/-) mice by both Th17 cells and neutrophils were the result of preferential production of IL-23/IL-17-axis cytokines by dendritic cells. Our study showed that gal3 negatively regulates IL-17A responses through inhibition of IL-23/IL-17-axis cytokine production by dendritic cells.
authors: Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei 10051, Taiwan.
authors: Sheng-Yang
authors: SY
authors: Wu
authors: Jhang-Sian
authors: JS
authors: Yu
authors: Fu-Tong
authors: FT
authors: Liu
authors: Shi-Chuen
authors: SC
authors: Miaw
authors: Betty A
authors: BA
authors: Wu-Hsieh
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism*; D006658:Histoplasma / Q000276:immunology*; D006660:Histoplasmosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D054884:Host-Pathogen Interactions / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000494:pharmacology; D053759:Interleukin-23 / Q000096:biosynthesis / Q000494:pharmacology; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology
chemical_list: D016207:Cytokines; D037502:Galectin 3; D020381:Interleukin-17; D053759:Interleukin-23