Motavalli Roza, Soltani-Zangbar Mohammad Sadegh, Fereydoonzadeh Khadijeh, Hajivalili Mahsa, Ahmadian Heris Javad, Kahroba Houman, Niknafs Bahram, Motavalli Khiavi Farhad, Dolati Sanam, Sadeghi Mohammadreza, Yousefi Mehdi, Etemadi Jalal
Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Mol Biol Rep. 2023 May;50(5):4097-4104. doi: 10.1007/s11033-023-08306-7. Epub 2023 Mar 6.
Chronic renal failure is mainly connected with high and low parathyroid hormone (PTH) levels and immunological impairments. The present study aimed to evaluate T helper 17 (Th17) cells as a crucial modulator of the immune system and skeletal homeostasis in hemodialysis patients with impaired intact PTH (iPTH).
In this research, blood samples were taken from ESRD patients with high (> 300 pg/mL), normal (150-300 pg/mL), and low (< 150 pg/mL) serum intact parathyroid hormone (iPTH( levels (n = 30 in each group). The frequency of Th17 (CD4 IL17) cells was evaluated by flow cytometry in each group. The expression levels of Th17 cell-related master transcription factors, cytokines in peripheral blood mononuclear cells (PBMC), and Th cells, and the level of the mentioned cytokines were determined in the supernatant of PBMCs.
The number of Th17 cells remarkably increased in subjects with high iPTH against low and normal iPTH. Also, RORɣt and STAT3 levels were significantly higher in high iPTH ESRD patients than in other groups in the expression of mRNA and protein levels. These findings are confirmed by evaluating the IL-17 and IL-23 in the supernatant of cultured PBMCs and isolated Th cells.
Our findings indicated that increased serum PTH levels in hemodialysis cases may be involved in increasing the differentiation of CD4 + cells to Th17 cells in PBMC.
慢性肾衰竭主要与甲状旁腺激素(PTH)水平的高低及免疫功能损害有关。本研究旨在评估辅助性T细胞17(Th17)细胞作为免疫系统和骨骼稳态的关键调节因子在血清完整甲状旁腺激素(iPTH)受损的血液透析患者中的作用。
本研究采集了终末期肾病(ESRD)患者的血样,这些患者的血清完整甲状旁腺激素(iPTH)水平分别为高(>300 pg/mL)、正常(150 - 300 pg/mL)和低(<150 pg/mL)(每组n = 30)。通过流式细胞术评估每组中Th17(CD4 IL17)细胞的频率。测定外周血单个核细胞(PBMC)中Th17细胞相关主要转录因子、细胞因子以及Th细胞的表达水平,并测定PBMC上清液中上述细胞因子的水平。
iPTH水平高的患者中Th17细胞数量相对于iPTH水平低和正常的患者显著增加。此外,iPTH水平高的ESRD患者中RORɣt和STAT3在mRNA和蛋白质水平的表达显著高于其他组。通过评估培养的PBMC和分离的Th细胞上清液中的IL - 17和IL - 23证实了这些发现。
我们的研究结果表明,血液透析患者血清PTH水平升高可能参与了PBMC中CD4 +细胞向Th17细胞分化的增加。