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Circulating Neutrophils of Nonalcoholic Steatohepatitis Patients Show an Activated Phenotype and Suppress T Lymphocytes Activity.
Journal of Immunology Research ( IF 4.1 ) Pub Date : 2020-06-30 , DOI: 10.1155/2020/4570219
Laura Antonucci 1 , Cristiana Porcu 1 , Eleonora Timperi 2 , Silvano Junior Santini 3 , Gino Iannucci 2 , Clara Balsano 1, 3
Affiliation  

Neutrophils or PolyMorphonuclear Neutrophils (PMNs) are key effector cells of the innate immune system and thanks to their remarkable plasticity, establish a cross talk with T cells modulating their survival and effector functions. During Nonalcoholic Steatohepatitis (NASH), the advanced form of hepatic steatosis or NAFL, PMNs infiltrate liver tissue, becoming a histological feature of NASH. Our aim was to evaluate the frequency of PMNs in NAFL and NASH patients in order to understand how they modulate the activity of circulating CD4+ and CD8+ T cells. In our cohort of patients, NASH patients displayed a higher frequency of circulating PMNs that was strongly correlated to liver enzymes, grade of steatosis, inflammation and fibrosis, the hepatocellular ballooning, and NAFLD Activity Score (NAS). Furthermore, even if ex vivo, in both groups of patients, PMNs shared the same phenotype of resting cells, after 24 hours of coculture with autologous CD4+ and CD8+ T cells, PMNs of NASH patients acquired a more active phenotype, becoming able to strongly inhibit proliferation and activation of CD4+ and CD8+ T cells. The higher ability of PMNs of NASH patients in suppressing CD4+ and CD8+ T cells, over time, might contribute in reducing the immunological defense of liver tissue against damages thus taking part in the progression of the NAFL disease toward NASH.

中文翻译:

非酒精性脂肪性肝炎患者的循环中性粒细胞表现出激活的表型并抑制T淋巴细胞活性。

中性粒细胞或polyMorphonuclear中性粒细胞(PMNs)是先天免疫系统的关键效应细胞,并且由于其非凡的可塑性,可与T细胞建立串扰,调节其存活和效应功能。在非酒精性脂肪性肝炎(NASH)期间,肝脂肪变性或NAFL的晚期形式,PMN浸润肝组织,成为NASH的组织学特征。我们的目的是评估NAFL和NASH患者中PMN的频率,以了解它们如何调节循环CD4 +和CD8 +的活性T细胞。在我们的患者队列中,NASH患者表现出较高的循环PMN频率,这与肝酶,脂肪变性,炎症和纤维化的程度,肝细胞球囊扩张以及NAFLD活动评分(NAS)密切相关。此外,即使在离体的情况下,两组患者中的PMNs也共享相同的静止细胞表型,与自体CD4 +和CD8 + T细胞共培养24小时后,NASH患者的PMNs表现出更活跃的表型,从而能够强烈抑制CD4 +和CD8 + T细胞的增殖和活化。NASH患者PMN抑制CD4 +和CD8 +的能力更高 随着时间的推移,T细胞可能有助于减少肝脏组织抵抗损伤的免疫防御能力,从而参与NAFL疾病向NASH的发展。
更新日期:2020-06-30
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