Galectin-3 negatively regulates dendritic cell production of IL-23/IL-17-axis cytokines in infection by Histoplasma capsulatum

Sheng Yang Wu, Jhang Sian Yu, Fu-Tong Liu, Shi Chuen Miaw, Betty A. Wu-Hsieh

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


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. Copyright

Original languageEnglish (US)
Pages (from-to)3427-3437
Number of pages11
JournalJournal of Immunology
Issue number7
StatePublished - Apr 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Immunology


Dive into the research topics of 'Galectin-3 negatively regulates dendritic cell production of IL-23/IL-17-axis cytokines in infection by Histoplasma capsulatum'. Together they form a unique fingerprint.

Cite this