Galectin-2 Suppresses Contact Allergy by Inducing Apoptosis in Activated CD8+ T Cells

Abstract

Galectins, a family of structurally related β-galactoside-binding proteins, are expressed by various cells of the immune systems and seem to be important for the regulation of immune responses and immune cell homeostasis. Since it has been demonstrated that galectin-2 regulates cell-mediated inflammatory bowel disease and colitis in mice, we intended to investigate the role of galectin-2 in inflammatory cutaneous T cell-mediated immune responses. To address this issue, groups of naive mice were sensitized to the contact allergen 2,4-dinitro-1-fluorobenzene and systemically treated with galectin-2 to analyze the effects of galectin-2 on contact allergy. Here we show that galectin-2 is expressed in murine skin and is up-regulated upon cutaneous inflammation. Interestingly, treatment of mice with galectin-2 significantly reduced the contact allergy response. This effect was long-lasting since rechallenge of galectin-2-treated mice after a 14-day interval still resulted in a decreased ear swelling. We were able to demonstrate that galectin-2 induced a reduction of MHC class I-restricted immune responses in the treated animals, which was mediated by the induction of apoptosis specifically in activated CD8+ T cells. Additionally, we report that the galectin-2-binding protein CD29 is up-regulated on the surface of activated CD8+ T cells compared with naive CD8+ T cells or CD4+ T cells, suggesting that increased galectin-2/CD29 signaling might be responsible for the proapoptotic effects of galectin-2 on activated CD8+ T cells. Taken together, these data indicate that galectin-2 may represent a novel therapeutic alternative for the treatment of CD8-mediated inflammatory disorders such as contact allergy.

Effects of genotype and dietary fish oil replacement with vegetable oil on the intestinal transcriptome and proteome of Atlantic salmon (Salmo salar)

“…Relevant to the above was the up-regulation of galectin 2 (LGALS2) in the proteome of salmon fed VO. Galectins are pleiotropic regulators of immune functions and are up-regulated by injury and infectious conditions, have well-recognized modulatory roles in mammalian intestinal inflammatory diseases, and their mode of action involves induction of apoptosis [65,66]. The lack of major effects on cell proliferation and only slight up-regulation of CASP3 and LGALS2 suggests that any contaminant doses experienced by the fish were unlikely to have caused any serious morphophysiological damage in the intestine.…”

Towards molecular mechanisms regulating the expression of galectins in cancer cells under microenvironmental stress conditions

“…It performs an anti-inflammatory function in the intestine, inducing the apoptosis of specific populations of T cells [53,54]. This lectin has been shown to move to the nucleus of fibroblastic cells exposed to physical (UV light), chemical (mitomycin C, serum withdrawal), or cell biological (coculture with stromal cells) treatment modalities [55].…”

Lowered expression of galectin-2 is associated with lymph node metastasis in gastric cancer

“…To date, 15 mammalian galectins have been identified in a wide variety of tissues and tumors, and it seems that they may play a critical role in the modulation of chronic inflammatory disorders, autoimmunity and cancer [14,15]. Of them, galectin-2 is structurally closely related to galectin-1 by sharing 43% amino acid sequence identity with galectin-1 [15,16].…”

“…Galectin-1 is expressed by a wide variety of cell types, while galectin-2 has a distinct expression profile primarily confined to the epithelial cells of the gastrointestinal tract [16,17]. It has been reported that galectin-2 suppresses contact allergy, ameliorates colitis, and plays a significant role in intestinal woundhealing processes by inducing apoptosis of T lymphocytes [15,16,18,19]. In contrast to galectin-1 and galectin-3, relatively few studies have examined the expression of galectin-2 in tumors in animals and humans [14,20] and only one study appears to have shown galectin-2 expression in GC [21].…”

“…To date, 15 mammalian galectins have been identified in a wide variety of tissues and tumors, and it seems that they may play a critical role in the modulation of chronic inflammatory disorders, autoimmunity and cancer [14,15]. Of them, galectin-2 is structurally closely related to galectin-1 by sharing 43% amino acid sequence identity with galectin-1 [15,16]. Galectin-1 is expressed by a wide variety of cell types, while galectin-2 has a distinct expression profile primarily confined to the epithelial cells of the gastrointestinal tract [16,17].…”