Peptidase inhibitor 16 identifies a human regulatory T-cell subset with reduced FOXP3 expression over the first year of recent onset type 1 diabetes.,European Journal of Immunology

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Peptidase inhibitor 16 identifies a human regulatory T-cell subset with reduced FOXP3 expression over the first year of recent onset type 1 diabetes.
European Journal of Immunology ( IF 4.5 ) Pub Date : 2019-06-05 , DOI: 10.1002/eji.201948094
Christoper M Hope _{1,

2} , John Welch _{3,

4} , Arunesh Mohandas ₃ , Stephen Pederson _{1,

5} , Danika Hill ₁ , Batjargal Gundsambuu _{1,

3} , Nicola Eastaff-Leung _{1,

3} , Randall Grosse ₃ , Suzanne Bresatz _{1,

3} , Grace Ang _{1,

3} , Michael Papademetrios ₃ , Heddy Zola _{3,

4} , Thomas Duhen ₆ , Daniel Campbell ₆ , Cheryl Y Brown ₁ , Doreen Krumbiegel ₃ , Timothy Sadlon ₂ , Jennefer J Couper ₄ , Simon C Barry _{1,

2,

3}

Affiliation

CD4+ T-cell subsets play a major role in the host response to infection, and a healthy immune system requires a fine balance between reactivity and tolerance. This balance is in part maintained by regulatory T cells (Treg), which promote tolerance, and loss of immune tolerance contributes to autoimmunity. As the T cells which drive immunity are diverse, identifying and understanding how these subsets function requires specific biomarkers. From a human CD4 Tconv/Treg cell genome wide analysis we identified peptidase inhibitor 16 (PI16) as a CD4 subset biomarker and we now show detailed analysis of its distribution, phenotype and links to Treg function in type 1 diabetes. To determine the clinical relevance of Pi16 Treg, we analysed PI16+ Treg cells from type 1 diabetes patient samples. We observed that FOXP3 expression levels declined with disease progression, suggesting loss of functional fitness in these Treg cells in Type 1 diabetes, and in particular the rate of loss of FOXP3 expression was greatest in the PI16+ve Treg. We propose that PI16 has utility as a biomarker of functional human Treg subsets and may be useful for tracking loss of immune function in vivo. The ability to stratify at risk patients so that tailored interventions can be applied would open the door to personalised medicine for Type 1 diabetes.

中文翻译：

肽酶抑制剂16可以识别人调节性T细胞亚群，与最近发作的1型糖尿病的第一年相比，FOXP3的表达降低。

CD4 + T细胞亚群在宿主对感染的反应中起主要作用，健康的免疫系统需要在反应性和耐受性之间达到良好的平衡。这种平衡在某种程度上由调节性T细胞（Treg）维持，调节性T细胞（Treg）促进耐受性，而免疫耐受性的丧失有助于自身免疫。由于驱动免疫力的T细胞是多种多样的，因此识别和理解这些亚群的功能需要特定的生物标记。从人类CD4 Tconv / Treg细胞全基因组分析中，我们确定了肽酶抑制剂16（PI16）作为CD4子集生物标志物，并且现在我们显示其在1型糖尿病中的分布，表型以及与Treg功能的联系的详细分析。为了确定Pi16 Treg的临床相关性，我们分析了来自1型糖尿病患者样品的PI16 + Treg细胞。我们观察到，FOXP3表达水平随疾病进展而下降，表明在1型糖尿病的这些Treg细胞中功能适应性的丧失，尤其是PI16 + ve Treg中FOXP3表达的丧失速率最大。我们提出PI16具有作为功能性人类Treg亚型的生物标志物的效用，可能对跟踪体内免疫功能的丧失有用。可以对高危患者进行分层，以便进行量身定制的干预措施，这将为1型糖尿病的个性化药物打开大门。我们提出PI16具有作为功能性人类Treg亚型的生物标志物的效用，可能对跟踪体内免疫功能的丧失有用。可以对高危患者进行分层，以便进行量身定制的干预措施，这将为1型糖尿病的个性化药物打开大门。我们提出PI16具有作为功能性人类Treg亚型的生物标志物的效用，可能对跟踪体内免疫功能的丧失有用。可以对高危患者进行分层，以便进行量身定制的干预措施，这将为1型糖尿病的个性化药物打开大门。

更新日期：2019-06-05

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