Background/Purpose: Defects of regulatory T cell (Tregs) mainly contribute to loss of tolerance to self-antigen which is significantly implicated in the pathogenesis of systemic lupus erythematosus (SLE). We investigated proportion of Tregs in the peripheral blood mononuclear cells (PBMCs) of patients with SLE and differentiation difference of induced Tregs in vitro under the presence or absence of endoplasmic reticulum (ER) stress, which is one of the causal factors triggering lupus flares, compared with that of healthy controls (HCs).

Methods: We isolated the PBMCs of 26 SLE patients and 26 HCs (Table 1). The percentage of CD4⁺CD25⁺FoxP3⁺ Tregs was analyzed using flow cytometry. The PBMCs were incubated with anti-CD3/CD28 beads, supplemented with transforming growth factor-¥â and interleukin-2 to induce differentiation of Tregs, with or without tunicamycin for 24 hours.

Results: The percentage of Tregs in the PBMCs of SLE patients was lower than that in the HCs (4.1 ¡¾ 1.0 versus 4.4 ¡¾ 1.5 %, p=0.5). The induced differentiation of Tregs increased in both groups, and the increased proportion was greater in the SLE group (327 ¡¾ 234 versus 221 ¡¾ 96%, p=0.04). Incubation with tunicamycin in the Tregs differentiation process also increased the proportion of Tregs in both groups (227 ¡¾ 186 versus 92 ¡¾ 57%, p=0.001), and the increased proportion was higher in the SLE group. We also compared the incremental differences between exposure of ER stress and no exposure of ER stress. In SLE patients, the smaller difference was observed (39 ¡¾ 46%) compared with HC group (73 ¡¾ 53%) with statistical significance (Figure 1).

Conclusion: The baseline percentage of Tregs was lower in SLE patients than in HCs. However, when Treg differentiation was induced, the differentiation was more increased in SLE group and incremental difference between under the condition of ER stress and absence of ER stress was also smaller in SLE group. The exaggerated differentiation of Tregs in SLE patients may reflect less susceptibility or more resistance to ER stress in SLE lymphocytes on the process of Tregs differentiation.

Table 1. Baseline Characteristics of SLE patients and HCs

Figure 1. Increased proportion and incremental difference of Induced Tregs in vitro with and without ER stress