儿童自身免疫性疾病中髓源性抑制细胞的含量

T. Radygina, Daria G. Kuptsova, S. Petrichuk, A. Potapov, N. Murashkin, L. M. Abdullaeva, O. Kurbatova, V. Tsvetkova
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引用次数: 0

摘要

髓源性抑制细胞(Myeloid-derived suppressor cells, MDSCs)在免疫应答调控中发挥重要作用。据报道,在患有自身免疫性疾病的成年患者中,它们的数量有所增加。自身免疫性疾病不同阶段的G-MDSCs、M-MDSCs和MDSCs(M-G-)都可能激活T细胞增殖,导致疾病进展,也可能抑制T细胞增殖,从而促进Treg分化。精氨酸酶-1 (Arg- 1)是MDSCs中的一种酶,可降低T淋巴细胞增殖所需的精氨酸浓度。我们的目的是评估自身免疫性疾病儿童中MDSCs群体的含量和MDSCs的功能活性。75名炎症性肠病(IBD)儿童,60名多发性硬化症(MS)儿童,69名牛皮癣(PS)儿童,62名年龄匹配的健康儿童纳入研究。采用流式细胞术检测MDSCs (CD3、CD19、CD56、HLA-DR)-、CD11b+和CD33+)、MDSCs亚群(表达CD14和CD15的M-MDSCs、G-MDSCs)的含量和Arg-1活性。IBD、MS和PS患者的MDSCs含量显著高于对照组,且与加重/缓解状态有关。在IBD、MS和PS的加重和缓解期,与健康儿童相比,MDSCs显著增加;在多发性硬化症加重的儿童中发现了最高的值(Me-3.5 (2.5-5.6) % MNC对Me-1.6 (0.9-2.5) % MNC, p 0.001)。MS患儿G-MDSC、M-MDSC含量明显高于健康儿童,MDSC(M-G-)含量明显低于健康儿童。与疾病缓解状态相比,MS加重时G-MDSCs的绝对数量增加(p = 0.022)。对于IBD患者,相对于缓解状态,MDSCs和M-MDSCs的百分比在病情加重时显著增加(p = 0.014和p = 0.045)。在IBD、MS和PS患者中,发现MDSCs中Arg-1活性显著增加,与疾病加重期相比,缓解期患者的MDSCs数量减少。在患有自身免疫性疾病的儿童中,发现MDSC人群增加。MDSCs中精氨酸酶-1的活性在缓解期增加,同时其数量减少。
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Content of myeloid-derived suppressor cells in autoimmune diseases in children
Myeloid-derived suppressor cells (MDSCs) play an important role in regulation of immune response. An increase in their number in adult patients with autoimmune diseases has been reported. G-MDSCs, M-MDSCs, and MDSCs(M-G-) at different stages of autoimmune disease may both activate T cell proliferation, leading to disease progression, or inhibit it, thus promoting Treg differentiation. Arginase-1 (Arg- 1) is an enzyme in MDSCs that reduces the concentration of arginine required for T lymphocyte proliferation. Our aim was to evaluate the content of MDSCs populations and functional activity of MDSCs in children with autoimmune diseases. 75 children with inflammatory bowel diseases (IBD), 60 children with multiple sclerosis (MS), 69 children with psoriasis (PS), 62 healthy age-matched children were included into the study. The content of MDSCs ((CD3, CD19, CD56, HLA-DR)-, CD11b+ and CD33+), subpopulations of MDSCs (M-MDSCs, G-MDSCs expressing CD14 and CD15), assessment of Arg-1 activity were performed by flow cytometry techniques. The content of MDSCs in patients with IBD, MS and PS was significantly higher than in the comparison group and depended on the state of exacerbation/remission. In exacerbation and remission of IBD, MS and PS, a significant increase of MDSCs was revealed when compared with healthy children; the highest values were found in children in exacerbation of MS (Me-3.5 (2.5-5.6) % MNC against Me-1.6 (0.9-2.5) % MNC, p 0.001). In patients with MS, the content of G-MDSC, M-MDSC was significantly higher, and MDSC(M-G-) was lower than in healthy children. An increase in absolute amounts of G-MDSCs was shown in MS exacerbation compared to the disease remission state (p = 0.022). For patients with IBD, a significant increase in percentage of MDSCs and M-MDSCs (p = 0.014 and p = 0.045, respectively) was obtained in exacerbation of the disease relative to remission state. In patients with IBD, MS, and PS, a significant increase in Arg-1 activity in MDSCs was found, with a decreased number of MDSCs in patients in remission compared to exacerbation phase of the disease. In children with autoimmune diseases, an increase in the MDSC populations was found. The activity of arginase-1 in MDSCs is increased in remission, along with a decrease in their numbers.
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