Galectin-3 is critical for the development of the allergic inflammatory response in a mouse model of atopic dermatitis

Jun Saegusa, Daniel K. Hsu, Huan Yuan Chen, Lan Yu, Agnes Fermin, Maxwell A Fung, Fu-Tong Liu

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Galectin-3 belongs to a family of β-galactoside-binding animal lectins expressed in several cell types, including epithelial and immune cells. To establish the role of galectin-3 in the development of allergic skin inflammation, we compared inflammatory skin responses of galectin-3-deficient (gal3-/-) and wild-type (gal3+/+) mice to epicutaneous sensitization with ovalbumin (OVA). OVA-treated gal3-/- mice exhibited markedly reduced epidermal thickening, lower eosinophil infiltration, and lower serum IgE levels compared with gal3+/+ mice. The former evoked lower interleukin-4, but higher interferon-γ, mRNA expression at OVA-treated skin sites. Moreover, gal3-/- splenocytes from OVA-sensitized mice secreted more interleukin-12 compared with gal3 +/+ splenocytes. In addition, antigen presentation by gal3 -/- dendritic cells to T cells in vitro were T helper cell (Th1)-polarized relative to presentation by gal3+/+ dendritic cells. When exposed to OVA, recipients engrafted with T cells from gal3-/- OVA-specific T cell receptor transgenic mice developed significantly reduced dermatitis and a markedly lower Th2 response compared with recipients of comparable gal3+/+ T cells. We conclude that galectin-3 is critical for the development of inflammatory Th2 responses to epicutaneously administered antigens; in its absence, mice develop a Th1-polarized response. This regulatory effect of galectin-3 on Th development is exerted at both the dendritic cell and T cell levels. Our studies suggest that galectin-3 may play an important role in the acute phase of human atopic dermatitis.

Original languageEnglish (US)
Pages (from-to)922-931
Number of pages10
JournalAmerican Journal of Pathology
Volume174
Issue number3
DOIs
StatePublished - Mar 2009

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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