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食物过敏和嗜酸性粒细胞性胃肠病中存在独特的 CRTH2+CD161+（peTh2）记忆 CD4+T 细胞细胞因子谱。

Distinct CRTH2+CD161+ (peTh2) memory CD4+ T-cell cytokine profiles in food allergy and eosinophilic gastrointestinal disorders.

机构信息

Human Eosinophil Section, LPD, NIAID, NIH, Bethesda, Maryland, USA.

Clinical Parasitology Section, LPD, NIAID, NIH, Bethesda, Maryland, USA.

出版信息

Clin Exp Allergy. 2023 Oct;53(10):1031-1040. doi: 10.1111/cea.14376. Epub 2023 Jul 24.

DOI:10.1111/cea.14376
PMID:37487654
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10592354/
Abstract

INTRODUCTION

Although IgE-mediated food allergy (FA) and eosinophilic gastrointestinal disorders (EGID) are clinically distinct and treated differently, pathogenic effector Th2 (peTh2) cells are implicated in the pathogenesis of both FA and EGID. The aim of this study was to better characterize peTh2 cells in the context of FA and EGID and the overlap between these two conditions.

METHODS

Peripheral blood peTh2 cells (CD3+CD4+CD27-CD49d+CRTH2+CD161+) were profiled by intracellular cytokine flow cytometry in the following patient cohorts: patients with FA alone (n = 8), FA and food-triggered EGID (EGID+FA+FT, n = 7), food-triggered EGID alone (EGID+FT, n = 7), EGID without FA or specific food triggers (ONLY_EGID, n = 9), and healthy volunteers (HV, n = 7). Overnight peripheral blood mononuclear cell (PBMC) culture supernatants were assessed for cytokine production by multiplex analysis.

RESULTS

CRTH2+CD161+ (peTh2) memory CD4+ T cells were significantly increased in both patients with FA and those with ALL_EGID (inclusive of EGID+FA+FT, EGID+FT and ONLY_EGID) when compared to HV. However, ALL_EGID patients, particularly those with EGID+FA+FT, had significantly elevated IL-5+IL-13+ peTh2 cells, whereas FA patients had significantly elevated IFN-γ or IL-17A-expressing peTh2 cells. This finding was supported by increased spontaneous IL-5 and IL-13 production in overnight cultures of PBMC from EGID+FA+FT patients compared to spontaneous IL-10 and IFN-γ production by PBMC from FA patients. FA patients had increased IL-9, IL-10, IL-17A, and IFN-γ production in overnight cultures of stimulated PBMC.

CONCLUSIONS

EGID and IgE-mediated FA share a common cell subtype defined by specific surface markers and termed CRTH2+CD161+ (peTh2) memory CD4+ T cells. However, the cytokine profiles of these CRTH2+CD161+ (peTh2) memory CD4+ T cells are markedly different between the two disorders.

摘要

简介

虽然 IgE 介导的食物过敏 (FA) 和嗜酸性粒细胞性胃肠病 (EGID) 在临床上是不同的，并且治疗方法也不同，但致病性效应 Th2 (peTh2) 细胞与 FA 和 EGID 的发病机制有关。本研究旨在更好地描述 FA 和 EGID 背景下的 peTh2 细胞，以及这两种疾病之间的重叠。

方法

通过细胞内细胞因子流式细胞术对以下患者队列的外周血 peTh2 细胞（CD3+CD4+CD27-CD49d+CRTH2+CD161+）进行分析：仅患有 FA 的患者（FA 组，n=8）、FA 合并食物触发的 EGID（EGID+FA+FT 组，n=7）、仅食物触发的 EGID（EGID+FT 组，n=7）、无 FA 或特定食物触发的 EGID（ONLY_EGID 组，n=9）和健康志愿者（HV 组，n=7）。通过多重分析评估过夜外周血单核细胞（PBMC）培养上清液的细胞因子产生情况。

结果

与 HV 相比，FA 患者和 ALL_EGID 患者（包括 EGID+FA+FT、EGID+FT 和 ONLY_EGID）的 CRTH2+CD161+（peTh2）记忆 CD4+T 细胞明显增加。然而，ALL_EGID 患者，特别是 EGID+FA+FT 患者，具有显著升高的 IL-5+IL-13+peTh2 细胞，而 FA 患者具有显著升高的 IFN-γ或 IL-17A 表达的 peTh2 细胞。这一发现得到了以下支持：与 FA 患者 PBMC 的自发 IL-10 和 IFN-γ产生相比，EGID+FA+FT 患者 PBMC 的 overnight 培养中自发 IL-5 和 IL-13 产生增加。FA 患者在刺激后的 PBMC overnight 培养中产生增加的 IL-9、IL-10、IL-17A 和 IFN-γ。

结论

EGID 和 IgE 介导的 FA 具有共同的细胞亚型，该细胞亚型由特定的表面标志物定义，并被称为 CRTH2+CD161+（peTh2）记忆 CD4+T 细胞。然而，这两种疾病之间的这些 CRTH2+CD161+（peTh2）记忆 CD4+T 细胞的细胞因子谱有明显的不同。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86ab/10592354/77177eaa35f7/nihms-1917783-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86ab/10592354/5ff2c8e1fc6d/nihms-1917783-f0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86ab/10592354/137c70e3d6c7/nihms-1917783-f0003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86ab/10592354/77177eaa35f7/nihms-1917783-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86ab/10592354/5ff2c8e1fc6d/nihms-1917783-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86ab/10592354/1d5c043955a7/nihms-1917783-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86ab/10592354/137c70e3d6c7/nihms-1917783-f0003.jpg
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