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

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.