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 journalArticle

36 Citations (Scopus)

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. Copyright

Original languageEnglish (US)
Pages (from-to)3427-3437
Number of pages11
JournalJournal of Immunology
Volume190
Issue number7
DOIs
StatePublished - Apr 1 2013
Externally publishedYes

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Galectin 3
Interleukin-23
Histoplasma
Interleukin-17
Dendritic Cells
Cytokines
Infection
Th17 Cells
Neutrophils
Histoplasmosis
Th1 Cells
Adoptive Transfer
Interleukin-12

ASJC Scopus subject areas

  • Immunology

Cite this

Galectin-3 negatively regulates dendritic cell production of IL-23/IL-17-axis cytokines in infection by Histoplasma capsulatum. / Wu, Sheng Yang; Yu, Jhang Sian; Liu, Fu-Tong; Miaw, Shi Chuen; Wu-Hsieh, Betty A.

In: Journal of Immunology, Vol. 190, No. 7, 01.04.2013, p. 3427-3437.

Research output: Contribution to journalArticle

Wu, Sheng Yang ; Yu, Jhang Sian ; Liu, Fu-Tong ; Miaw, Shi Chuen ; Wu-Hsieh, Betty A. / Galectin-3 negatively regulates dendritic cell production of IL-23/IL-17-axis cytokines in infection by Histoplasma capsulatum. In: Journal of Immunology. 2013 ; Vol. 190, No. 7. pp. 3427-3437.
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