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嗜酸粒细胞性胃炎中的局部 2 型免疫。

Local type 2 immunity in eosinophilic gastritis.

机构信息

Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.

Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.

出版信息

J Allergy Clin Immunol. 2023 Jul;152(1):136-144. doi: 10.1016/j.jaci.2023.01.021. Epub 2023 Feb 7.

Abstract

BACKGROUND

Eosinophilic gastritis (EoG) associates with type 2 immunity. However, the type 2 cytokine cellular source, gastric T-cell composition, and gastric T-cell relationship (or relationships) with disease pathology remain understudied.

OBJECTIVE

We defined gastric T-cell populations and their association with histologic and endoscopic EoG pathology.

METHODS

Gastric biopsy samples (n = 6 EoG, n = 7 control) were subjected to histologic, endoscopic, and flow cytometry analyses. In a complementary cohort (n = 83 EoG), IL4, IL5, and IL13 mRNA levels were correlated with EoG pathologic parameters.

RESULTS

Gastric biopsy samples contained CD3 T cells that were mainly CD8; the CD8/CD4 ratio was comparable in EoG and control biopsy samples (5.7 ± 3.0 and 4.3 ± 0.6, respectively; P = .28). Gastric regulatory T (CD3CD4FOXP3) and T2 (CD3CD4GATA3) cell levels were increased in EoG versus controls (2-fold, P < .05 and 10-fold, P < .001, respectively) and correlated with gastric eosinophil levels (r = 0.63, P < .05 and r = 0.85, P < .001, respectively), endoscopic pathology (r = 0.56, P < .01; r = 0.84, P < .001, respectively), and histopathology (r = 0.72, P < .01; r = 0.82, P < .01, respectively). Cytokine-positive, most notably IL-4, T2 cell levels strongly correlated with histologic and endoscopic scores (r = 0.82, P < .0001 and r = 0.78, P < .0001, respectively). In an independent EoG cohort (n = 83), bulk gastric IL4, IL5, and IL13 mRNA levels correlated with histologic score (r = 0.22, P < .005; r = 0.54, P < .0001; and r = 0.36, P < .0001, respectively) and endoscopic score (r = 0.27, P < .001; r = 0.40, P < .0001; and r = 0.35, P < .0001, respectively).

CONCLUSIONS

EoG is a T2 cell-associated disease featuring increased gastric type 2 cytokine-producing CD3CD4GATA3T2 cells that strongly correlate with disease pathologies.

摘要

背景

嗜酸性粒细胞性胃炎(EoG)与 2 型免疫有关。然而,2 型细胞因子的细胞来源、胃 T 细胞组成以及胃 T 细胞与疾病病理学之间的关系仍有待研究。

目的

我们定义了胃 T 细胞群及其与组织学和内镜 EoG 病理学的关系。

方法

对胃活检样本(EoG n=6,对照组 n=7)进行组织学、内镜和流式细胞术分析。在一个补充队列(EoG n=83)中,IL4、IL5 和 IL13 mRNA 水平与 EoG 病理参数相关。

结果

胃活检样本中含有主要为 CD8 的 CD3 T 细胞;EoG 和对照组活检样本中的 CD8/CD4 比值相似(分别为 5.7±3.0 和 4.3±0.6;P=0.28)。与对照组相比,EoG 中胃调节性 T(CD3CD4FOXP3)和 T2(CD3CD4GATA3)细胞水平增加(2 倍,P<0.05 和 10 倍,P<0.001,分别),并与胃嗜酸性粒细胞水平相关(r=0.63,P<0.05 和 r=0.85,P<0.001,分别)、内镜病理(r=0.56,P<0.01;r=0.84,P<0.001,分别)和组织病理学(r=0.72,P<0.01;r=0.82,P<0.01,分别)。细胞因子阳性,尤其是 IL-4,T2 细胞水平与组织学和内镜评分高度相关(r=0.82,P<0.0001 和 r=0.78,P<0.0001,分别)。在一个独立的 EoG 队列(n=83)中,胃内 IL4、IL5 和 IL13 mRNA 水平与组织学评分相关(r=0.22,P<0.005;r=0.54,P<0.0001;r=0.36,P<0.0001,分别)和内镜评分(r=0.27,P<0.001;r=0.40,P<0.0001;r=0.35,P<0.0001,分别)。

结论

EoG 是一种与 2 型 T 细胞相关的疾病,其特征为胃内产生 2 型细胞因子的 CD3CD4GATA3T2 细胞增多,与疾病病理学密切相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab32/10330288/15441cc21f00/nihms-1872334-f0002.jpg

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