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 beta-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-gamma, 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.
Saegusa
Jun
J
Department of Dermatology, University of California, Davis, School of Medicine, 3301 C Street, Suite 1400, Sacramento, CA 95816, USA.
Hsu
Daniel K
DK
Chen
Huan-Yuan
HY
Yu
Lan
L
Fermin
Agnes
A
Fung
Maxwell A
MA
Liu
Fu-Tong
FT
D019264:Adoptive Transfer; D000818:Animals; D001706:Biopsy; D003433:Crosses, Genetic; D003876:Dermatitis, Atopic / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D037502:Galectin 3 / Q000172:deficiency / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D037502:Galectin 3; D010047:Ovalbumin