Inhibitory control of endothelial galectin‐1 onin vitroandin vivolymphocyte trafficking

Abstract

Galectin-1 (Gal-1) is a beta-galactoside-binding protein, the expression of which is increased in endothelial cells on exposure to proinflammatory stimuli. Through binding of several receptors (CD7, CD45, and CD43) Gal-1 is known to induce apoptosis of activated T lymphocytes, an effect thought to mediate the beneficial effects it exerts in various inflammatory models. The data presented here highlights another function for Gal-1, that of a negative regulator of T-cell recruitment to the endothelium under both physiological and pathophysiological conditions. We have shown, using siRNA to knockdown Gal-1 in endothelial cells, that endogenous Gal-1 limits T-cell capture, rolling, and adhesion to activated endothelial cells under flow. Furthermore, the reverse effect is observed when exogenous human recombinant Gal-1 is added to activated endothelial monolayers whereby a dramatic reduction in lymphocyte recruitment is seen. These findings are corroborated by studies in Gal-1 null mice in which homing of wild-type (WT) T lymphocytes is significantly increased to mesenteric lymph nodes and to the inflamed paw in a model of delayed-type hypersensitivity. In conclusion, mimicking endothelial Gal-1 actions would be a novel strategy for controlling aberrant T-cell trafficking, hence for the development of innovative anti-inflammatory therapeutics.

Psoriasis in humans is associated with down‐regulation of galectins in dendritic cells

“…However, recent studies acknowledge the importance of anti-inflammatory signals that counterbalance the inflammatory response. Galectins are implicated in the negative regulation of the immune response, participating in processes such as immune cell proliferation [28], apoptosis [29], cellular adhesion and migration [30][31][32], and modulation of the interactions between T cells and APCs [33].…”

Endogenous galectin-1 enforces class I–restricted TCR functional fate decisions in thymocytes

“…Alternatively, gal-1 could be controlling homing of CD8␣␣ IEL to the intestine, consistent with studies implicating gal-1 in T-cell trafficking during inflammation. 47 We previously reported that gal-1 has the capacity to differentially regulate distinct downstream TCR signal transduction events and functional outcomes. 18 Gal-1 may alter TCR coupling to downstream signaling pathways (including ERK activation) by positioning surface glycoprotein or glycolipid ligands capable of influencing TCR binding and signal transduction.…”

A role for MC3R in modulating lung inflammation

“…Whilst for TH2 responses in the asthmatic lung activation of integrins on circulating eosinophils followed by tethering and rolling on bronchial endothelial cells [4] with increases in IL-4 and IL-5 leading to further activation and subsequent transmigration [5]. To aid in the resolution of this response a number of endogenous modulators of inflammation are produced including annexin 1 [6], galectin [7], lipoxins [8] and melanocortins [9,10] and these have been shown to inhibit leukocyte trafficking and help prevent tissue damage.…”