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Am J Pathol. 2013 Oct;183(4):1209-1222. doi: 10.1016/j.ajpath.2013.06.017. Epub 2013 Aug 3.

Galectin-3 modulates Th17 responses by regulating dendritic cell cytokines.

Author information

1
Department of Dermatology, University of California, Davis, School of Medicine, Sacramento, California.
2
Department of Dermatology, University of California, Davis, School of Medicine, Sacramento, California; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
3
Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
4
Graduate Institute of Immunology, National Taiwan University, College of Medicine, Taipei, Taiwan.
5
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
6
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.

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.

PMID:
23916470
PMCID:
PMC3791687
DOI:
10.1016/j.ajpath.2013.06.017
[Indexed for MEDLINE]
Free PMC Article

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