Galectin-3 modulates Th17 responses by regulating dendritic cell cytokines

Agnes Fermin Lee, Huan Yuan Chen, Lei Wan, Sheng Yang Wu, Jhang Sian Yu, Annie C. Huang, Shi Chuen Miaw, Daniel K. Hsu, Betty A. Wu-Hsieh, Fu-Tong Liu

Research output: Contribution to journalArticle

28 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1209-1222
Number of pages14
JournalAmerican Journal of Pathology
Volume183
Issue number4
DOIs
StatePublished - Oct 2013

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Fermin Lee, A., Chen, H. Y., Wan, L., Wu, S. Y., Yu, J. S., Huang, A. C., Miaw, S. C., Hsu, D. K., Wu-Hsieh, B. A., & Liu, F-T. (2013). Galectin-3 modulates Th17 responses by regulating dendritic cell cytokines. American Journal of Pathology, 183(4), 1209-1222. https://doi.org/10.1016/j.ajpath.2013.06.017