Altered Cell Surface N-Glycosylation of Resting and Activated T Cells in Systemic Lupus Erythematosus.

Enikő Szabó,Ákos Hornung,Ágnes Czibula,László Kovács,Márta Bocskai,Éva Monostori

doi:10.3390/ijms20184455

Abstract

Altered cell surface glycosylation in congenital and acquired diseases has been shown to affect cell differentiation and cellular responses to external signals. Hence, it may have an important role in immune regulation; however, T cell surface glycosylation has not been studied in systemic lupus erythematosus (SLE), a prototype of autoimmune diseases. Analysis of the glycosylation of T cells from patients suffering from SLE was performed by lectin-binding assay, flow cytometry, and quantitative real-time PCR. The results showed that resting SLE T cells presented an activated-like phenotype in terms of their glycosylation pattern. Additionally, activated SLE T cells bound significantly less galectin-1 (Gal-1), an important immunoregulatory lectin, while other lectins bound similarly to the controls. Differential lectin binding, specifically Gal-1, to SLE T cells was explained by the increased gene expression ratio of sialyltransferases and neuraminidase 1 (NEU1), particularly by elevated ST6 beta-galactosamide alpha-2,6-sialyltranferase 1 (ST6GAL1)/NEU1 and ST3 beta-galactoside alpha-2,3-sialyltransferase 6 (ST3GAL6)/NEU1 ratios. These findings indicated an increased terminal sialylation. Indeed, neuraminidase treatment of cells resulted in the increase of Gal-1 binding. Altered T cell surface glycosylation may predispose the cells to resistance to the immunoregulatory effects of Gal-1, and may thus contribute to the pathomechanism of SLE.

Highlights

Numerous congenital and acquired diseases show altered cell surface glycosylation, including several types of cancer and autoimmune syndromes [1,2]
We have recently demonstrated that activated T cells from patients with active systemic lupus erythematosus (SLE) are resistant to the apoptotic effect of Gal-1 [20], and we suggested that this finding is relevant to the immunoregulatory dysfunction observed in SLE
To understand the distinct lectin binding, Gal-1, to SLE T cells, we found that the terminal sialylation increased in the autoimmune cells, and neuraminidase treatment resulted in a remarkable increase in Gal-1 binding

Summary

Introduction

Numerous congenital and acquired diseases show altered cell surface glycosylation, including several types of cancer and autoimmune syndromes [1,2]. One of the major effects of Gal-1 in immunoregulation is the induction of apoptosis of the activated T cell subpopulations Th1 and Th17, whereas Th2 and Treg cell functions are promoted by Gal-1 [12,13]. This selectivity is caused by the differences in surface glycosylation of various T cell subtypes [9]. Lactosamine sequences, required for Gal-1 binding, are synthesized by specific glycosyltransferases, such as beta-N-acetylglucosaminyltransferases and beta-galactosyltransferases The expression of such enzymes controls T cell susceptibility to Gal-1-driven apoptosis [19]. To understand the distinct lectin binding, Gal-1, to SLE T cells, we found that the terminal sialylation increased in the autoimmune cells, and neuraminidase treatment resulted in a remarkable increase in Gal-1 binding

Results

Patients

Lectin Binding Assay

Neuraminidase Treatment

Statistical Analysis