Mucosal-Associated Invariant T Cells Are Depleted and Exhibit Altered Chemokine Receptor Expression and Elevated Granulocyte Macrophage-Colony Stimulating Factor Production During End-Stage Renal Disease.
Mucosal-Associated Invariant T Cells Are Depleted and Exhibit Altered Chemokine Receptor Expression and Elevated Granulocyte Macrophage-Colony Stimulating Factor Production During End-Stage Renal Disease.
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DOI：
10.3389/fimmu.2018.01076
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发表时间：
2018
影响因子：
7.3
通讯作者：
Kiazyk SA
中科院分区：
文献类型：
--
作者：
Juno JA;Waruk JLM;Wragg KM;Mesa C;Lopez C;Bueti J;Kent SJ;Ball TB;Kiazyk SA
终末期肾病（ESRD）与传染病易感性增加相关，包括结核分枝杆菌（Mtb）感染。粘膜相关不变性T （MAIT）细胞可识别多种细菌（包括结核分枝杆菌）产生的维生素B代谢物，并可能在提供抗肺部结核感染的保护性免疫中发挥重要作用。迄今为止，对ESRD患者的MAIT细胞频率、表型或功能知之甚少。通过表面标记表达或MR1四聚体结合鉴定MAIT细胞，用多色流式细胞术对20名ESRD参与者和20名健康对照者进行了表征。在PMA/离子霉素、IL-12/IL-18或大肠杆菌刺激后，测定体外MAIT细胞表型和细胞因子的产生。单核细胞表型和血浆c反应蛋白/炎症细胞因子水平通过流式细胞术、ELISA和多重头阵列进行量化。通过表型和四聚体分析，与对照组相比，ESRD患者外周血MAIT细胞明显减少，并且表现出CXCR3表达缺失，CCR6和CXCR6表达增加。ESRD还与MAIT pma诱导的细胞因子产生从IFNγ产生转向粒细胞巨噬细胞集落刺激因子（GM-CSF）分泌，以及大肠杆菌刺激的肿瘤坏死因子α表达的丧失有关。IFNγ表达的丧失与年龄、Tbet和Eomes表达的改变以及炎症血浆细胞因子水平有关。外周血MAIT细胞的缺失和相关的组织归巢受体表达和GM-CSF产生的变化可能导致允许细菌复制的免疫环境，特别是在肺部。
End-stage renal disease (ESRD) is associated with an increased susceptibility to infectious diseases, including infection with Mycobacterium tuberculosis (Mtb). Mucosal-associated invariant T (MAIT) cells recognize vitamin B metabolites produced by many bacterial species, including Mtb, and may play an important role in providing protective immunity against tuberculosis infection in the lung. To date, little is known about MAIT cell frequency, phenotype, or function in ESRD patients. MAIT cells, identified by surface marker expression or MR1 tetramer binding, were characterized in 20 ESRD and 20 healthy control participants by multicolor flow cytometry. Ex vivo MAIT cell phenotype and cytokine production following PMA/ionomycin, IL-12/IL-18, or Escherichia coli stimulation were determined. Monocyte phenotype and plasma C-reactive protein/inflammatory cytokine levels were quantified by flow cytometry, ELISA, and multiplex bead array. Peripheral blood MAIT cells were significantly depleted among ESRD patients compared to controls by both phenotypic and tetramer analysis and exhibited a loss of CXCR3 expression coupled to increased expression of CCR6 and CXCR6. ESRD was also associated with a shift in MAIT PMA-induced cytokine production away from IFNγ production and toward granulocyte macrophage-colony stimulating factor (GM-CSF) secretion, and a loss of E. coli-stimulated tumor necrosis factor α expression. Loss of IFNγ expression was associated with a combination of age, alterations in Tbet and Eomes expression, and inflammatory plasma cytokine levels. The loss of peripheral blood MAIT cells and associated shifts in tissue homing receptor expression and GM-CSF production may contribute to an immune environment that is permissive to bacterial replication, particularly in the lungs.
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影响因子：
4
作者：
Gherardin NA;Souter MN;Koay HF;Mangas KM;Seemann T;Stinear TP;Eckle SB;Berzins SP;d'Udekem Y;Konstantinov IE;Fairlie DP;Ritchie DS;Neeson PJ;Pellicci DG;Uldrich AP;McCluskey J;Godfrey DI
通讯作者：
Godfrey DI
影响因子：
4.2
作者：
Hu, H. Y.;Wu, C. Y.;Chu, D.
通讯作者：
Chu, D.
影响因子：
32.4
作者：
Croxford, Andrew L.;Lanzinger, Margit;Becher, Burkhard
通讯作者：
Becher, Burkhard
影响因子：
4.4
作者：
Campbell, JJ;Brightling, CE;Wardlaw, AJ
通讯作者：
Wardlaw, AJ
影响因子：
16.6
作者：
Al-Mossawi MH;Chen L;Fang H;Ridley A;de Wit J;Yager N;Hammitzsch A;Pulyakhina I;Fairfax BP;Simone D;Yi Y;Bandyopadhyay S;Doig K;Gundle R;Kendrick B;Powrie F;Knight JC;Bowness P
通讯作者：
Bowness P