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The tolerogenic peptide hCDR1 immunomodulates cytokine and regulatory molecule gene expression in blood mononuclear cells of primary Sjogren's syndrome patients
Clinical Immunology ( IF 4.5 ) Pub Date : 2018-05-04 , DOI: 10.1016/j.clim.2018.05.001
Zev Sthoeger , Amir Sharabi , Ilan Asher , Heidy Zinger , Rafael Segal , Gene Shearer , Ori Elkayam , Edna Mozes

Primary Sjogren‘s syndrome (pSS) is an autoimmune disease characterized by lymphocytic infiltration of exocrine glands. We investigated whether the tolerogenic peptide, hCDR1, that ameliorates lupus manifestations would have beneficial effects on pSS as well. The in vitro effects of hCDR1 on gene expression of pro-inflammatory cytokines and regulatory molecules were tested in peripheral blood mononuclear cells (PBMC) of 16 pSS patients. hCDR1, but not a control peptide, significantly reduced gene expression of IL-1β, TNF-α, MX-1 and BlyS and up-regulated immunosuppressive (TGF-β, FOXP3) molecules in PBMC of pSS patients. hCDR1 did not affect gene expression in patients with rheumatoid arthritis and anti-phospholipid syndrome. Further, hCDR1 up-regulated the expression of Indoleamine 2,3-dioxygenase (IDO) via elevation of TGF-β. IDO inhibition led to a significant decrease in the expression of FOXP3 which is crucial for the induction of T regulatory cells. Thus, hCDR1 is potential candidate for the specific treatment of pSS patients.



中文翻译:

致耐受性肽hCDR1免疫调节原发性干燥综合征患者血液单核细胞中的细胞因子和调节分子基因表达

原发性干燥综合征(pSS)是一种自身免疫性疾病,其特征是外分泌腺的淋巴细胞浸润。我们研究了是否能改善狼疮表现的致耐受性肽hCDR1也会对pSS产生有益影响。在16例pSS患者的外周血单核细胞(PBMC)中测试了hCDR1对促炎细胞因子和调节分子基因表达的体外影响。hCDR1(而非对照肽)可显着降低pSS患者PBMC中IL-1β,TNF-α,MX-1和BlyS的基因表达,并上调免疫抑制(TGF-β,FOXP3)分子。hCDR1不会影响类风湿关节炎和抗磷脂综合征患者的基因表达。此外,hCDR1通过提高TGF-β上调了吲哚胺2,3-二加氧酶(IDO)的表达。IDO抑制导致FOXP3表达的显着降低,这对于诱导T调节细胞至关重要。因此,hCDR1是pSS患者特异性治疗的潜在候选者。

更新日期:2018-05-04
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