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细胞因子信号转导蛋白 3 和 5 的抑制剂可能可以区分慢性鼻-鼻窦炎中 Th 细胞的极化。

Suppressor of Cytokine Signaling Proteins 3 and 5 Potentially Delineate Polarization of Th cells in Chronic Rhinosinusitis.

机构信息

ENT and Head and Neck Research Center and Department, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran.

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Yale J Biol Med. 2024 Jun 28;97(2):165-177. doi: 10.59249/HZFN2950. eCollection 2024 Jun.

Abstract

: Chronic rhinosinusitis (CRS) is an inflammatory condition classified into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP). Th cells manage inflammatory cells in CRS. Suppressor of Cytokine Signaling (SOCS) proteins regulate Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in Th cells by polarizing toward Th1, Th2, and Th17 cells. This study evaluated the levels of SOCS1,3,5 in CRS patients to find associations with Th cells. : In this cross-sectional study, 20 CRSwNP patients, 12 CRSsNP patients, and 12 controls participated. The infiltration of CD4 T cells was determined using immunohistochemistry. The expression of specific transcription factors and SOCS proteins was assessed using real-time PCR. Cytokine levels were evaluated using ELISA. SOCS protein levels were investigated using western blot analysis. : The expression of SOCS3 increased in the CRSwNP group compared to CRSsNP and control groups ( <0.001). SOCS3 protein levels increased in the CRSwNP group compared to CRSsNP ( <0.05) and control ( <0.001) groups. Although there was a significant difference in SOCS5 expression between CRSsNP and control groups, SOCS5 protein levels were significantly different between CRSsNP and control ( <0.001) and CRSwNP ( <0.05) groups. : Targeted therapies may be suggested for CRS by modulating SOCS3 and SOCS5 proteins that are responsible for polarization of Th cells toward Th2 or Th1 cells, respectively. JAK-STAT pathway targeting, which encompasses numerous cells, can be limited to SOCS proteins to more effectively orchestrate Th cell differentiation.

摘要

慢性鼻-鼻窦炎(CRS)是一种炎症性疾病,分为伴有鼻息肉的慢性鼻-鼻窦炎(CRSwNP)和不伴有鼻息肉的慢性鼻-鼻窦炎(CRSsNP)。辅助性 T 细胞(Th 细胞)调控 CRS 中的炎症细胞。抑制细胞因子信号转导(SOCS)蛋白通过向 Th1、Th2 和 Th17 细胞极化来调节 Janus 激酶(JAK)-信号转导子和转录激活子(STAT)通路。本研究评估了 CRS 患者 SOCS1、3、5 的水平,以寻找与 Th 细胞的关联。

在这项横断面研究中,20 例 CRSwNP 患者、12 例 CRSsNP 患者和 12 例对照者参与研究。采用免疫组织化学法检测 CD4 T 细胞浸润。采用实时 PCR 评估特定转录因子和 SOCS 蛋白的表达。采用 ELISA 评估细胞因子水平。采用 Western blot 分析检测 SOCS 蛋白水平。

与 CRSsNP 组和对照组相比,CRSwNP 组 SOCS3 的表达增加( <0.001)。与 CRSsNP 组相比,CRSwNP 组 SOCS3 蛋白水平升高( <0.05)和对照组( <0.001)。虽然 CRSsNP 组和对照组之间 SOCS5 的表达存在显著差异,但 SOCS5 蛋白水平在 CRSsNP 组和对照组( <0.001)和 CRSwNP 组( <0.05)之间存在显著差异。

通过调节 SOCS3 和 SOCS5 蛋白,可以针对负责 Th 细胞向 Th2 或 Th1 细胞极化的 SOCS3 和 SOCS5 蛋白,为 CRS 提出靶向治疗方法。针对包含众多细胞的 JAK-STAT 通路,可以将其限定为 SOCS 蛋白,以更有效地协调 Th 细胞分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30a8/11202107/0d7ce722fcab/yjbm_97_2_165_g01.jpg

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