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MAIT cell activation in adolescents is impacted by bile acid concentrations and body weight.
Clinical & Experimental Immunology ( IF 4.6 ) Pub Date : 2020-02-17 , DOI: 10.1111/cei.13423
A Mendler 1 , A Pierzchalski 1 , M Bauer 1 , S Röder 1 , A Sattler 2 , M Standl 3 , M Borte 4 , M von Bergen 5, 6 , U Rolle-Kampczyk 5 , G Herberth 1
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Bile acids (BAs) are produced by liver hepatocytes and were recently shown to exert functions additional to their well-known role in lipid digestion. As yet it is not known whether the mucosal-associated invariant T (MAIT) cells, which represent 10-15% of the hepatic T cell population, are affected by BAs. The focus of the present investigation was on the association of BA serum concentration with MAIT cell function and inflammatory parameters as well as on the relationship of these parameters to body weight. Blood samples from 41 normal weight and 41 overweight children of the Lifestyle Immune System Allergy (LISA) study were analyzed with respect to MAIT cell surface and activation markers [CD107a, CD137, CD69, interferon (IFN)-γ, tumor necrosis factor (TNF)-α] after Escherichia coli stimulation, mRNA expression of promyelocytic leukemia zinc finger protein (PLZF) and major histocompatibility complex class I-related gene protein (MR1), the inflammatory markers C-reactive protein (CRP), interleukin (IL)-8 and macrophage inflammatory protein (MIP)-1α as well as the concentrations of 13 conjugated and unconjugated BAs. Higher body weight was associated with reduced MAIT cell activation and expression of natural killer cell marker (NKp80) and chemokine receptor (CXCR3). BA concentrations were positively associated with the inflammatory parameters CRP, IL-8 and MIP-1α, but were negatively associated with the number of activated MAIT cells and the MAIT cell transcription factor PLZF. These relationships were exclusively found with conjugated BAs. BA-mediated inhibition of MAIT cell activation was confirmed in vitro. Thus, conjugated BAs have the capacity to modulate the balance between pro- and anti-inflammatory immune responses.

中文翻译:

青少年的MAIT细胞活化受胆汁酸浓度和体重的影响。

胆汁酸(BAs)是由肝肝细胞产生的,最近被证明除了在脂质消化中的众所周知的作用外,还发挥其他功能。迄今为止,还不知道代表肝T细胞群体10-15%的粘膜相关不变T(MAIT)细胞是否受BAs影响。本研究的重点是BA血清浓度与MAIT细胞功能和炎症参数的关系,以及这些参数与体重的关系。对生活方式免疫系统过敏(LISA)研究的41名正常体重和41名超重儿童的血液样本进行了MAIT细胞表面和激活标记[CD107a,CD137,CD69,干扰素(IFN)-γ,肿瘤坏死因子(TNF)的分析)-α]刺激大肠杆菌后,早幼粒细胞白血病锌指蛋白(PLZF)和主要组织相容性复合物I类相关基因蛋白(MR1),炎症标志物C反应蛋白(CRP),白介素(IL)-8和巨噬细胞炎症蛋白(MIP)的mRNA表达1α以及13种共轭和未共轭BA的浓度。更高的体重与减少的MAIT细胞活化以及自然杀伤细胞标志物(NKp80)和趋化因子受体(CXCR3)的表达有关。BA浓度与炎症参数CRP,IL-8和MIP-1α正相关,但与活化的MAIT细胞和MAIT细胞转录因子PLZF负相关。这些关系仅在共轭BA中发现。体外证实了BA介导的对MAIT细胞活化的抑制。从而,
更新日期:2020-02-17
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