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Decreased circulating CXCR3 + CCR9+T helper cells are associated with elevated levels of their ligands CXCL10 and CCL25 in the salivary gland of patients with Sjögren's syndrome to facilitate their concerted migration.
Scandinavian Journal of Immunology ( IF 4.1 ) Pub Date : 2019-12-13 , DOI: 10.1111/sji.12852
Sofie L M Blokland 1, 2 , Andreas Kislat 3 , Bernhard Homey 3 , Glennda M Smithson 4 , Aike A Kruize 1 , Timothy R D J Radstake 1, 2 , Joel A G van Roon 1, 2
Affiliation  

CCR9 + T helper (Th) cells can induce Sjögren-like symptoms in mice and both CCR9 + Th cells and their ligand CCL25 are increased in the salivary glands of primary Sjögren's syndrome (pSS) patients. Increased circulating CCR9 + Th cells are present in pSS patients. CCR9 + Th cells are hyperresponsive to IL-7, secrete high levels of IFN-γ, IL-21, IL-17 and IL-4 and potently stimulate B cells in both patients and healthy individuals. Our aim was to study co-expression of chemokine receptors on CCR9 + Th cells and whether in pSS this might differentially affect CCR9 + Th cell frequencies. Frequencies of circulating CCR9 + and CCR9- Th cells co-expressing CXCR3, CCR4, CCR6 and CCR10 were studied in pSS patients and healthy controls. CCL25, CXCL10, CCL17, CCL20 and CCL27 mRNA and protein expression of salivary gland tissue of pSS and non-Sjögren's sicca (non-SS) patients was assessed. Chemotaxis assays were performed to study migration induced by CXCL10 and CCL25. Higher expression of CXCR3, CCR4 and CCR6 but not CCR10 was observed on CCR9 + Th cells as compared to cells lacking CCR9. Decreased frequencies of circulating memory CCR9 + CXCR3+ Th cells were found in pSS patients, which was most pronounced in the effector memory subset. Increased salivary gland CCL25 and CXCL10 expression significantly correlated and both ligands functioned synergistically based on in vitro induced chemotaxis. Decreased memory CXCR3 + CCR9+ Th cells in blood of pSS patients may be due to a concerted action of overexpressed ligands at the site of inflammation in the salivary glands facilitating their preferential migration and positioning in the lymphocytic infiltrates.

中文翻译:

干燥的CXCR3 + CCR9 + T辅助细胞的减少与干燥综合征患者唾液腺中配体CXCL10和CCL25的水平升高有关,以促进其协调的迁移。

CCR9 + T辅助(Th)细胞可在小鼠中诱发Sjögren样症状,在原发性Sjögren综合征(pSS)患者的唾液腺中,CCR9 + Th细胞及其配体CCL25均增加。pSS患者中循环CCR9 + Th细胞增多。CCR9 + Th细胞对IL-7过敏,分泌高水平的IFN-γ,IL-21,IL-17和IL-4,并有效刺激患者和健康个体的B细胞。我们的目的是研究趋化因子受体在CCR9 + Th细胞上的共表达,以及在pSS中是否可能差异影响CCR9 + Th细胞的频率。在pSS患者和健康对照组中研究了共表达CXCR3,CCR4,CCR6和CCR10的循环CCR9 +和CCR9-Th细胞的频率。CCL25,CXCL10,CCL17,评估了pSS和非Sjögren's Sicca(非SS)患者唾液腺组织的CCL20和CCL27 mRNA和蛋白表达。进行趋化性测定以研究由CXCL10和CCL25诱导的迁移。与缺乏CCR9的细胞相比,在CCR9 + Th细胞上观察到CXCR3,CCR4和CCR6的高表达,但没有CCR10。在pSS患者中发现循环记忆CCR9 + CXCR3 + Th细胞的频率降低,这在效应记忆子集中最为明显。唾液腺CCL25和CXCL10表达的增加显着相关,并且两个配体均基于体外诱导的趋化性发挥协同作用。
更新日期:2019-11-01
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