Increased expression of human T-cell immunoglobulin- and mucin-domain-containing molecule-4 in peripheral blood mononuclear cells from patients with system lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease. Innate and adaptive immunity cooperatively contribute to the development of SLE. Antigen-presenting cells (APCs) have been suggested to link innate and adaptive immunity. T-cell immunoglobulin- and mucin-domain-containing molecule-4 (Tim-4; also known as Timd4), expressed primarily on the surface of APCs, is a member of the TIM family, a recently described group of molecules that have received much attention as potential regulators of the immune system. In this study, we used quantitative real-time reverse transcription-polymerase chain reaction to examine the mRNA expression of Tim-4 in peripheral blood mononuclear cells (PBMCs) from SLE patients and further analyzed the correlation between the expression of Tim-4 and Tim-1 (a potential ligand for Tim-4) in PBMCs and serum tumor necrosis factor (TNF)-alpha levels. The results showed that Tim-4 mRNA expression in PBMCs was significantly higher in SLE patients than in healthy controls, especially those patients in the active phase of disease. Moreover, Tim-4 mRNA levels were closely correlated with Tim-1 mRNA levels in PBMCs and with serum TNF-alpha levels in SLE patients but not in the control group. Taken together, these results demonstrate that Tim-4 may be involved in the pathogenesis of SLE.

Figure 1

Tim-4 mRNA expression levels in PBMCs from SLE patients and healthy controls. Tim-4 mRNA expression levels in PBMCs were determined by real-time RT-PCR. The results show that the mean expression levels of Tim-4 mRNA in PBMCs from SLE patients were significantly higher than those in healthy controls (a). We divided the SLE patients into two groups: active phase (SLEDAI>10) or inactive phase (SLEDAI<5) and found that Tim-4 mRNA levels were significantly higher in patients in the active phase than in those in the inactive phase (b). Each point represents an individual patient and medians are marked for each group. PBMCs, peripheral blood mononuclear cells; RT-PCR, reverse transcription polymerase chain reaction; SLE, systemic lupus erythematosus; SLEDAI, Systemic Lupus Erythematosus Disease Activity Index; Tim-4, T-cell immunoglobulin- and mucin-domain-containing molecule-4.

Figure 2

Correlation analysis of Tim-1 and Tim-4 levels in PBMCs from SLE patients and healthy controls. Tim-1 and Tim-4 mRNA expression levels were analyzed by real-time RT-PCR and correlation analysis were performed. A positive correlation between Tim-1 and Tim-4 mRNA levels was found in SLE patients (a), but there was no correlation in the healthy control group (b). Each point represents an individual patient. PBMCs, peripheral blood mononuclear cells; RT-PCR, reverse transcription polymerase chain reaction; SLE, systemic lupus erythematosus; Tim-1, T-cell immunoglobulin- and mucin-domain-containing molecule-1; Tim-4, T-cell immunoglobulin- and mucin-domain-containing molecule-4.

Figure 3

Serum TNF-α levels and positive correlation with Tim-4 mRNA expression levels in PBMCs from SLE patients. TNF-α levels in serum were determined by ELISA. The concentrations of TNF-α in SLE patients were significantly higher than those in healthy controls (a). There was a positive correlation between serum TNF-α concentrations and Tim-4 mRNA levels in PBMCs from SLE patients (b). Each point represents an individual patient and the median for each group is shown. PBMCs, peripheral blood mononuclear cells; SLE, systemic lupus erythematosus; Tim-4, T-cell immunoglobulin- and mucin-domain-containing molecule-4; TNF, tumor necrosis factor.