The regulating role of galectin-9 in immune cell populations

Abstract

Galectin-9 (gal-9) is a protein that belongs to the galectin family. Gal-9 is expressed in cells of the innate and adaptive immune system, including lymphocytes, dendritic cells, giant salivary cells, eosinophils and T cells, etc. In different immune cells, the role of gal-9 is different. Gal-9 can induce the proliferation and activation of immune cells, and also promote the apoptosis of immune cells. This effect of gal-9 affects the occurrence and development of a variety of immune-related diseases, such as the invasion of pathogenic microorganisms, immune escape of tumor cells, and inflammatory response. Thus, understanding the biological roles of gal-9 in innate and adaptive immunity may be essential for autoimmune diseases treatment and diagnosis to improve patient quality of life. In this review, we aim to summarize current research on the regulatory roles of gal-9 in human immune system and potential inducers and inhibitors of gal-9, which may provide new strategies for immune diseases therapies.

Keywords: T cell; galectin-9; immune; inhibitors; strategies.

FIGURE 1

The structural classification of galectins is divided into three types. The prototype galectins possess one CRD and exist in a dimeric form. The chimeric galectin-3 has a non-CRD structural domain at the N-terminus and a CRD structural domain at the C-terminus. The non-CRD structural domain of galectin-3 participates in the assembly of pentamers. The tandem repeat galectins have two CRDs that are connected by a short linker peptide.

FIGURE 2

The possible effects of gal-9 on the activation of the innate immune cells. a: Gal-9 not only promotes the activation of NK cells to release IFN-γ, but also promotes the polarization of F-actin of NK cells. b: Gal-9 promotes the polarization of M1 macrophages towards M2 macrophages, which is detrimental to clear pathogens. c: Gal-9 promotes neutrophils recruitment to the site of inflammation and neutrophils degranulation, thereby clearing pathogens. d: Gal-9 binds to IgE on mast cells, and this interaction prevents the formation of IgE antigen complexes and reduces allergic reactions. e: Gal-9 can promote the adhesion of eosinophils to fibroblasts and prolong their function. f: Gal-9 promotes DCs maturation, thereby activating T cells. In addition, gal-9 promotes cytokine release by interacting with Vamp-3.

FIGURE 3

Schematic diagram illustrating the effects of gal-9 on the function of the CD4⁺ T cell subsets. In the presence of gal-9, the balance of the number of Th1, Th2, Th17 and Treg cells changes. Gal-9 can promote apoptosis of Th1 cells by up-regulating caspase-1 and down-regulating CD11b⁺Ly-6G⁺. The reduction of Th1 cells leads to reduced IFN-γ and TNF-α release, which in turn exacerbates pathogen infection and tumor progression. Gal-9 promotes the release of large amounts of IL-10 by Treg cells, which can further inhibit Th1 activation, as well as alleviate autoimmune diseases. Gal-9 can also reduce the IL-17 release by inhibiting the activation of Th17 cells, which alleviates autoimmune disease. The thickness of the line represents the strength of the promoting or inhibiting effect.