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 language | English (US) |
|---|---|
| Pages (from-to) | 922-931 |
| Number of pages | 10 |
| Journal | American Journal of Pathology |
| Volume | 174 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2009 |
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ASJC Scopus subject areas
- Pathology and Forensic Medicine
Cite this
Galectin-3 is critical for the development of the allergic inflammatory response in a mouse model of atopic dermatitis. / Saegusa, Jun; Hsu, Daniel K.; Chen, Huan Yuan; Yu, Lan; Fermin, Agnes; Fung, Maxwell A; Liu, Fu-Tong.
In: American Journal of Pathology, Vol. 174, No. 3, 03.2009, p. 922-931.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Galectin-3 is critical for the development of the allergic inflammatory response in a mouse model of atopic dermatitis
AU - Saegusa, Jun
AU - Hsu, Daniel K.
AU - Chen, Huan Yuan
AU - Yu, Lan
AU - Fermin, Agnes
AU - Fung, Maxwell A
AU - Liu, Fu-Tong
PY - 2009/3
Y1 - 2009/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=62549134859&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=62549134859&partnerID=8YFLogxK
U2 - 10.2353/ajpath.2009.080500
DO - 10.2353/ajpath.2009.080500
M3 - Article
C2 - 19179612
AN - SCOPUS:62549134859
VL - 174
SP - 922
EP - 931
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 3
ER -