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组织浸润淋巴细胞分析揭示了乳糜泻患者在无麸质饮食后十二指肠“免疫生态位”的巨大改变。

Tissue-infiltrating lymphocytes analysis reveals large modifications of the duodenal "immunological niche" in coeliac disease after gluten-free diet.

机构信息

Institute of Internal Medicine, Catholic University, Rome, Italy.

出版信息

Clin Transl Gastroenterol. 2012 Dec 13;3(12):e28. doi: 10.1038/ctg.2012.22.

DOI:10.1038/ctg.2012.22
PMID:23324655
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3535075/
Abstract

OBJECTIVES

The role of T lymphocytes in the pathogenesis of Celiac disease (CD) is well established. However, the mechanisms of T-cell involvement remain elusive. Little is known on the distribution of T subpopulations: T-regulatory (Treg), Th17, CD103, and CD62L cells at disease onset and after gluten-free diet (GFD). We investigated the involvement of several T subpopulations in the pathogenesis of CD.

METHODS

We studied T cells both in the peripheral blood (PB) and the tissue-infiltrating lymphocytes (TILs) from the mucosa of 14 CD patients at presentation and after a GFD, vs. 12 controls.

RESULTS

Our results extend the involvement of Treg, Th1, and Th17 cells in active CD inflammation both in the PB and at the TILs. At baseline, Tregs, Th1, and Th17 cells are significantly higher in active CD patients in TILs and PB. They decreased after diet. Moreover, CD62L+ TILs were increased at diagnosis as compared with GFD patients.

CONCLUSIONS

Our data show significant modifications of the above-mentioned subpopulations both in the PB and TILs. The increase of suppressive Tregs in active CD both in the PB and TILs is intriguing. T lymphocytes are known to have a crucial role in the pathogenesis of CD. We have shown that gluten trigger results in systemic recruitment of T lymphocytes, the unbalance between pro-inflammatory and anti-inflammatory populations and the increase of CD62L+ T cells in TILs. Our results delineate a more complete picture of T-cell subsets in active vs. GFD disease. Our data of T-cell subpopulations, combined with known data on cytokine production, support the concept that duodenal micro-environment acts as an immunological niche and this recognition may have an important role in the diagnosis, prognosis and therapeutical approach of CD.

摘要

目的

T 淋巴细胞在乳糜泻(CD)发病机制中的作用已得到充分证实。然而,T 细胞参与的机制仍不清楚。关于 T 细胞亚群(T 调节细胞、Th17、CD103 和 CD62L 细胞)在发病时和无麸质饮食(GFD)后的分布知之甚少。我们研究了几种 T 细胞亚群在 CD 发病机制中的作用。

方法

我们研究了 14 例 CD 患者在发病时和 GFD 后外周血(PB)和黏膜浸润淋巴细胞(TILs)中的 T 细胞,以及 12 例对照者的 T 细胞。

结果

我们的结果扩展了 Treg、Th1 和 Th17 细胞在 PB 和 TIL 中活跃的 CD 炎症中的作用。在基线时,活跃的 CD 患者的 TIL 和 PB 中的 Treg、Th1 和 Th17 细胞显著升高。饮食后减少。此外,与 GFD 患者相比,诊断时 CD62L+TIL 增加。

结论

我们的数据显示,上述亚群在 PB 和 TIL 中均有显著改变。在 PB 和 TIL 中活跃的 CD 中,抑制性 Treg 的增加令人关注。T 淋巴细胞在 CD 的发病机制中起着至关重要的作用。我们已经表明,麸质触发导致 T 淋巴细胞的全身募集,促炎和抗炎群体之间的失衡,以及 TIL 中 CD62L+T 细胞的增加。我们的结果描绘了活跃的 CD 疾病与 GFD 疾病之间 T 细胞亚群的更完整图景。我们的 T 细胞亚群数据,结合已知的细胞因子产生数据,支持十二指肠微环境作为免疫生态位的概念,这一认识可能在 CD 的诊断、预后和治疗方法中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94e4/3535075/bb6aca3c0d31/ctg201222f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94e4/3535075/7e301a28fd61/ctg201222f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94e4/3535075/81c2049ae117/ctg201222f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94e4/3535075/bb6aca3c0d31/ctg201222f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94e4/3535075/7e301a28fd61/ctg201222f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94e4/3535075/81c2049ae117/ctg201222f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94e4/3535075/bb6aca3c0d31/ctg201222f3.jpg

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