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. 2018 Jul 5;131(13):1527-1532.
doi: 10.4103/0366-6999.235110.

Increased Macroautophagy in Interferon-Gamma-Producing T Cells from Patients with Newly Diagnosed Systemic Lupus Erythematosus

Xiong-Yan Luo  1 , Jia-Li Yuan  2 , Jing Liu  3 , Cai-Nan Luo  4 , Ming-Hui Yang  3 , Qin Wei  5 , Min Yang  1 , Yong Chen  2 , Yi Liu  1 , Guo-Hua Yuan  3
Affiliations

Increased Macroautophagy in Interferon-Gamma-Producing T Cells from Patients with Newly Diagnosed Systemic Lupus Erythematosus

Xiong-Yan Luo et al. Chin Med J (Engl). .

Abstract
in English, Chinese

Background: Imbalance of interferon-gamma (IFN-γ), interleukin (IL)-4, and IL-17 producing by T cells is confirmed to contribute to the pathogenesis of systemic lupus erythematosus (SLE). Autophagy is now emerging as a core player in the development and the function of the immune system. Therefore, we investigated the autophagic behavior in IFN-γ-, IL-4-, and IL-17-producing T cells from patients with SLE.

Methods: Thirty patients with SLE and 25 healthy controls matched for gender and age were recruited between September 2016 and May 2017. The autophagic levels in IFN-γ+ T cells, IL-4+ T cells, and IL-17+ T cells from patients with newly diagnosed SLE and healthy controls were measured using flow cytometry. The plasma levels of IFN-γ were determined by enzyme-linked immunosorbent assay in SLE patients and healthy controls. Unpaired t-tests and the nonparametric Mann-Whitney U-test were used to compare data from patients with SLE and controls. Spearman's rank correlation coefficient was applied for calculation of the correlation between parallel variables in single samples.

Results: Our results showed increased percentage of autophagy in IFN-γ+ T cells from patients with SLE and healthy controls ([8.07 ± 2.72]% vs. [3.76 ± 1.67]%, t = 5.184, P < 0.001), but not in IL-4+ T cells or IL-17+ T cells (P > 0.05) as compared to healthy donors. Moreover, the plasma levels of IFN-γ in SLE patients were significantly higher than those in healthy controls ([68.9 ± 29.1] pg/ml vs. [24.7 ± 17.6] pg/ml, t = 5.430, P < 0.001). Moreover, in SLE patients, the percentage of autophagy in IFN-γ+ T cells was positively correlated with the plasma levels of IFN-γ (r = 0.344, P = 0.046), as well as the disease activity of patients with SLE (r = 0.379, P = 0.039).

Conclusion: The results indicate that autophagy in IFN-γ+ T cells from SLE patients is activated, which might contribute to the persistence of T cells producing IFN-γ, such as Th1 cells, and consequently result in the high plasma levels of IFN-γ, and then enhance the disease activity of SLE.

新发系统性红斑狼疮患者分泌干扰素-γ的T细胞自噬水平增高摘要背景：已证实T细胞产生的干扰素(IFN)-γ,白细胞介素(IL)-4和IL-17比例失衡在系统性红斑狼疮（systemic lupus erythematosus，SLE）发病过程中发挥重要作用。自噬在促进免疫系统发育及维持免疫系统功能方面至关重要。因此，我们探讨SLE患者外周血分泌IFN-γ、 IL-4 或IL-17 的T细胞中自噬发生情况。 方法：从2016年9月至2017年5月招募30例新诊断的SLE患者及与其性别年龄匹配的25例健康对照者。通过流式细胞术检测SLE组和健康对照组外周血IFN-γ+细胞、IL-4+T及IL-17+ T细胞自噬水平。通过酶联免疫吸附实验（ELISA）检测SLE组和健康对照组血清IFN-γ 水平。未配对t检验和非参数Mann-Whitney U 检验用于SLE组和健康对照组之间的比较，Spearman检验用于检测变量之间的相关性。 结果：结果显示SLE患者IFN-γ+ T细胞自噬活性较健康对照组增高([8.07 ± 2.72] % vs [3.76 ± 1.67] %, t=5.184, p<0.001)，但IL-4+ T细胞或 IL-17+ T细胞自噬发生率在两组均无统计学差异（P>0.05）。进一步研究发现，SLE患者血浆IFN-γ水平明显高于健康对照组([68.9±29.1]pg/ml vs [24.7±17.6]pg/ml, t=5.430, p<0.001)。而且SLE患者IFN-γ+ T细胞自噬发生率与血清IFN-γ水平（r=0.344，P=0.046）和疾病活动度呈正相关(r=0.379, p=0.039)。 结论：SLE患者IFN-γ+ T细胞自噬活性增高，这可能有助于产生IFN-γ T细胞如Th1细胞持续存在，并导致血清IFN-γ水平增高，进而促使SLE患者病情活跃。.

Keywords: Autophagy; Lupus Erythematosus; Systemic; T Helper cells.

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Conflict of interest statement

There are no conflicts of interest

Figures

Figure 1
Figure 1
Detection of autophagy in IFN-γ+, IL-4+, and IL-17+ T cells from SLE patients and healthy controls. (a) Representative 2-color dot plots from analysis of autophagy and intracellular cytokines by flow cytometry. Numbers in dot plots indicate the percentage of autophagic cells. (b) Summary of autophagy in IFN-γ+, IL-4+, and IL-17+ T cells. Data are presented as means ± standard deviation of independent experiments performed in T cells from healthy controls (n = 25) and from SLE patients (n = 30). *SLE patients versus healthy controls, t = 5.184, P < 0.001. LC3: Microtubule-associated protein light chain 3; IFN: Interferon; IL-4: Interleukin-4; SLE: Systemic lupus erythematosus.
Figure 2
Figure 2
Correlation between circulating IFN-γ levels and percentage of autophagy in IFN-γ+ T cells from SLE patients (r = 0.344, P = 0.046). IFN-γ: Interferon-gamma; SLE: Systemic lupus erythematosus.
Figure 3
Figure 3
Correlation between the SLEDAI score and the percentage of autophagic cells in SLE patients (r = 0.379, P = 0.039). SLE: Systemic lupus erythematosus; SLEDAI: Systemic Lupus Erythematosus Disease Activity Index.
See this image and copyright information in PMC

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