Centre International de Recherche en Infectiologie (CIRI), Univ Lyon, Institut national de la santé et de la recherche médical (Inserm), U1111, Université Claude Bernard Lyon 1, Centre National de Recherche Scientifique (CNRS), UMR5308, Ecole National Supérieur (ENS) de Lyon, Lyon, France.
Department of Gastroenterology, Lyon-Sud Hospital, University Claude Bernard Lyon 1 and Hospices Civils de Lyon, Pierre-Bénite, France.
Front Immunol. 2022 Nov 4;13:864353. doi: 10.3389/fimmu.2022.864353. eCollection 2022.
We aimed to analyze circulating CD4 T cell subsets and cytokines during the course of Crohn's disease (CD).
CD4 T cell subsets, ultrasensitive C-reactive protein (usCRP), and various serum cytokines (IL-6, IL-8, IL-10, IL-13, IL-17A, IL-23, TNFα, IFNγ, and TGFβ) were prospectively monitored every 3 months for 1 year, using multicolor flow cytometry and an ultrasensitive Erenna method in CD patients in remission at inclusion. Relapse occurred in 35 out of the 113 consecutive patients (31%). For patients in remission within 4 months prior to relapse and at the time of relapse, there was no significant difference in Th1, Th17, Treg, and double-positive CD4 T cell subsets co-expressing either IFNγ and FOXP3, IL-17A and FOXP3, or IFNγ and IL-17A. On the contrary, in patients who remained in remission, the mean frequency and number of double-positive IL-17AFOXP3 CD4 T cells and the level of usCRP were significantly higher ( ≤ 0.01) 1 to 4 months prior to relapse. At the time of relapse, only the IL-6 and usCRP levels were significantly higher ( ≤ 0.001) compared with those patients in remission. On multivariate analysis, a high number of double-positive IL-17AFOXP3 CD4 T cells (≥1.4 cells/mm3) and elevated serum usCRP (≥3.44 mg/L) were two independent factors associated with risk of relapse.
Detection of circulating double-positive FOXP3IL-17A CD4 T cell subsets supports that T cell plasticity may reflect the inflammatory context of Crohn's disease. Whether this subset contributes to the pathogenesis of CD relapse needs further studies.
本研究旨在分析克罗恩病（CD）患者病程中的循环 CD4 T 细胞亚群和细胞因子。
采用多色流式细胞术和超敏 Erenna 法，对纳入时处于缓解期的 113 例连续 CD 患者，每 3 个月监测 1 年 CD4 T 细胞亚群、超敏 C 反应蛋白（usCRP）和各种血清细胞因子（IL-6、IL-8、IL-10、IL-13、IL-17A、IL-23、TNFα、IFNγ 和 TGFβ）。35 例患者出现复发（31%）。复发前 4 个月内及复发时处于缓解期的患者，Th1、Th17、Treg 及同时表达 IFNγ 和 FOXP3、IL-17A 和 FOXP3 或 IFNγ 和 IL-17A 的双阳性 CD4 T 细胞亚群无显著差异。相反，在持续缓解的患者中，1 至 4 个月前复发时，双阳性 IL-17AFOXP3 CD4 T 细胞的平均频率和数量以及 usCRP 水平显著升高（≤0.01）。复发时，与缓解期患者相比，仅 IL-6 和 usCRP 水平显著升高（≤0.001）。多变量分析显示，双阳性 IL-17AFOXP3 CD4 T 细胞数量高（≥1.4 个/ mm3）和血清 usCRP 升高（≥3.44mg/L）是与复发风险相关的两个独立因素。
循环双阳性 FOXP3IL-17A CD4 T 细胞亚群的检测支持 T 细胞可塑性可能反映克罗恩病的炎症状态。该亚群是否有助于 CD 复发的发病机制需要进一步研究。
