Galectins are a family of ��-galactoside-binding proteins.They can bind to and engage cell-surface glycans, thereby affecting a variety of cellular processes, but can also function intracellularly in a glycan-independent fashion. Galectin-1 and -9 have been documented to have immunosuppressive functions through induction of apoptosis in T cells, by engaging cell surface glycoproteins. Administration of recombinant galectin-1 and -9 in mice has been shown to suppress certain inflammatory and autoimmune responses. Mice deficient in galectin-1 or -9 have greater pathological responses in autoimmune disease models. Endogenous galectin-3 inhibits apoptosis in T cells by functioning intracellularly and also suppresses cytokine production in these cells by functioning at the immunological synapse through interacting with Alix, a component of endosomal sorting complex required for transport (ESCRT). In addition, galectin-3 can drive the Th cell response to the Th1 and Th17 directions by suppressing production of IL-12 (a key promoter of Th1 polarization) and IL-6 and IL-23 (promoters of Th17 polarization) by dendritic cells. In contrast to mice deficient in galectin-1 or -9, galectin-3-deficient mice have lower pathological responses in a number of inflammatory disease models.
Galectin-7 is highly expressed in stratified epithelia, including epidermis, but is down-regulated in psoriasis. Using microarray and deep-sequencing analyses, we found galectin-7 positively and negatively regulates miR-203 and miR-146a expression, respectively. We demonstrated that galectin-7 i) suppresses keratinocyte proliferation through the JNK1-miR-203-p63 pathway; and ii) suppresses production of inflammatory mediators by keratinocytes through the miR-146a-MAPK/ERK pathway.
Galectins can bind to cytosolic glycans presented as a danger signal when cells are infected by intracellular microbes. We found galectin-3 accumulated around LM that had escaped from phagosomes through binding to host glycans on the membrane of ruptured phagosomes that initially contained the bacteria. Moreover, our results suggest that through this mechanism, galectin-3 suppresses autophagy and promotes inflammasome activation induced by Listeria infection. Because a large number of substances can cause damage in intracellular vesicles, galectins may have broad implications in modulating responses resulting from sensing glycans displayed on damaged vesicles, including inflammatory responses.
