Expression of Human TIM‐1 and TIM‐3 on Lymphocytes from Systemic Lupus Erythematosus Patients

Abstract

The T‐cell immunoglobulin‐ and mucin‐domain‐containing molecules (TIMs) comprise a new family of cell surface molecules expressed on T cells. TIM‐3 is expressed on T helper type 1 (Th1) cells and implicated in the pathogenesis of Th1‐driven auto‐ and allo‐immune diseases. TIM‐1 is suggested to act as a co‐stimulatory molecule for all T cells, but with potentially stronger effects on Th2 than Th1 cells and is associated with Th2‐related immune diseases. However, the TIM molecules have not been investigated in the systemic lupus erythematosus (SLE). In this study, we examined the expression of TIM‐1 and TIM‐3 on peripheral blood mononuclear cells from SLE patients using quantitative real‐time RT‐PCR. An increased TIM‐1 expression was detected in SLE patients, which correlates with interleukin‐10 expression. We also found that there was a significant increase in the expression of TIM‐1 in SLE patients with quite active disease (SLE disease activity index > 6), indicating that TIM‐1 expression might be related to active clinical phases. In contrast, TIM‐3 expression remained normal in SLE patients with low statistical power (34.89%). However, the expression of TIM‐3 ligand, galectin‐9 increased in SLE patients indicating an enhanced engagement of TIM‐3 with its ligand in SLE, which may result in a decreased regulatory T‐cell function as shown by the decreased expression of FoxP3 and TGF‐β1 in SLE. These data suggest that TIM‐1 and TIM‐3/TIM‐3L are involved in the pathogenesis of SLE.

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

“…22 In a previous report, increased levels of Tim-1 were detected in SLE patients, which correlated with IL-10 expression. 40 However, we failed to detect any significant difference in Tim-1 mRNA levels in PBMCs from SLE patients versus healthy controls. This discrepancy may be due to differences in the SLEDAI of patients involved in each study: in the previous report, 17 out of 19 SLE patients had a SLEDAI higher than 5, while in the present study most patients (19/25) had a SLEDAI lower than 5.…”

Sex Differences in Autoimmune Disease from a Pathological Perspective

“…92 In another study, TIM-1 expression on peripheral blood mononuclear cells from SLE patients (associated with Th2 responses) correlated significantly with disease activity whereas TIM-3 expression (associated with Th1 responses) did not. 93 …”

T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) mediates natural killer cell suppression in chronic hepatitis B

“…T cell immunoglobulin-and mucin-domain-containing molecule-3 (Tim-3) plays a pivotal role in immune regulation and tolerance induction [11][12][13][14][15][16][17][18][19][20][21][22][23]. Engagement of Tim-3 by galectin-9 negatively regulates IFN-c secretion and influences the ability to induce T cell tolerance in both mice and humans [14,16].…”

“…Engagement of Tim-3 by galectin-9 negatively regulates IFN-c secretion and influences the ability to induce T cell tolerance in both mice and humans [14,16]. Recent studies have shown that Tim-3 is differentially expressed in innate versus adaptive immune cells, and that the ligation of Tim-3 can induce distinct signaling events, which may influence a range of inflammatory conditions [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30].…”