探索淋巴细胞的CD26-/lo亚群在哮喘表型和严重程度中的作用：一种表达原型粒细胞蛋白的新型CD4+T细胞亚群
2024/09/29
摘要
背景：哮喘病理可能导致幼稚/记忆淋巴细胞比例的变化，可以通过评估表面CD26（二肽基肽酶4/DPP4）水平来评估。
目的：本研究旨在探究哮喘表型/严重程度与不同淋巴细胞群中CD26-/lo、CD26int和CD26hi亚群相对频率的关系。
方法：本研究采用流式细胞术检测不同表型/严重程度的健康（N=30）和哮喘（N=119）受试者外周血样本中CD4+效应T细胞（Teff）、总CD4+淋巴细胞、γδ-T细胞、NK细胞和NKT细胞中CD26-/lo、CD26int和CD26hi亚群的比例。本研究采用K-means聚类分析，并通过LC-MS/MS和免疫荧光进一步表征了CD4+CD26-/lo-Teff细胞亚群。
结果：聚类分析根据临床和流式细胞数据将受试者分为四组，其中两组具有相反的炎症表型（即中性粒细胞型与嗜酸性粒细胞型）。中性粒细胞型哮喘表现为CD4-CD26hi细胞减少，与全身炎症呈负相关。嗜酸性粒细胞型哮喘表现为CD26-/lo亚群普遍增多。具体而言，哮喘患者中CD4+CD26-/lo-Teff增多，尤其是在过敏患者中，该亚群蛋白质组学特征为TEM/TEMA，表明固有蛋白（如MPO和RNASE2）和细胞骨架/细胞外基质（如MMP9和ACTN1）蛋白水平上调。免疫荧光检测证实CD4+T细胞存在非典型蛋白，且与CD4+T淋巴细胞相比，CD4+CD26-/lo-Teff中的“花状”核和MMP9/RNASE2水平富集。
结论：不同淋巴细胞亚群中的CD26表达水平与哮喘表型/严重程度相关。表达嗜酸性粒细胞/中性粒细胞特异性固有蛋白的CD4+CD26-/loTEMRA细胞可能是维持成人过敏性哮喘长期炎症的决定因素。
Exploring CD26-/lo subpopulations of lymphocytes in asthma phenotype and severity: A novel CD4+ T cell subset expressing archetypical granulocyte proteins.
Vázquez-Mera S, Martelo-Vidal L, Miguéns-Suárez P, Bravo SB, Saavedra-Nieves P, Arias P, Ferreiro-Posse A, Vázquez-Lago J, Salgado FJ, González-Barcala FJ, Nieto-Fontarigo JJ.
Abstract
BACKGROUND:Asthma pathology may induce changes in naïve/memory lymphocyte proportions assessable through the evaluation of surface CD26 (dipeptidyl peptidase 4/DPP4) levels.
OBJECTIVE:Our aim was to investigate the association of asthma phenotype/severity with the relative frequency of CD26-/lo, CD26int and CD26hi subsets within different lymphocyte populations.
METHODS:The proportion of CD26-/lo, CD26int and CD26hi subsets within CD4+ effector T cells (Teff), total CD4- lymphocytes, γδ-T cells, NK cells and NKT cells was measured in peripheral blood samples from healthy (N = 30) and asthma (N = 119) donors with different phenotypes/severities by flow cytometry. We performed K-means clustering analysis and further characterised the CD4+CD26-/lo Teff cell subset by LC-MS/MS and immunofluorescence.
RESULTS:Cluster analysis including clinical and flow cytometry data resulted in four groups, two of them with opposite inflammatory profiles (neutrophilic vs. eosinophilic). Neutrophilic asthma presented reduced CD4-CD26hi cells, which negatively correlated with systemic inflammation. Eosinophilic asthma displayed a general expansion of CD26-/lo subsets. Specifically, CD4+CD26-/lo Teff expansion was confirmed in asthma, especially in atopic patients. Proteomic characterisation of this subset with a TEM/TEMRA phenotype revealed upregulated levels of innate (e.g. MPO and RNASE2) and cytoskeleton/extracellular matrix (e.g. MMP9 and ACTN1) proteins. Immunofluorescence assays confirmed the presence of atypical proteins for CD4+ T cells, and an enrichment in 'flower-like' nuclei and MMP9/RNASE2 levels in CD4+CD26-/lo Teff compared to CD4+ T lymphocytes.
CONCLUSION: There is an association between CD26 levels in different lymphocyte subsets and asthma phenotype/severity. CD4+CD26-/lo TEMRA cells expressing innate proteins specific to eosinophils/neutrophils could be determinant in sustaining long-term inflammation in adult allergic asthma.
背景：哮喘病理可能导致幼稚/记忆淋巴细胞比例的变化，可以通过评估表面CD26（二肽基肽酶4/DPP4）水平来评估。
目的：本研究旨在探究哮喘表型/严重程度与不同淋巴细胞群中CD26-/lo、CD26int和CD26hi亚群相对频率的关系。
方法：本研究采用流式细胞术检测不同表型/严重程度的健康（N=30）和哮喘（N=119）受试者外周血样本中CD4+效应T细胞（Teff）、总CD4+淋巴细胞、γδ-T细胞、NK细胞和NKT细胞中CD26-/lo、CD26int和CD26hi亚群的比例。本研究采用K-means聚类分析，并通过LC-MS/MS和免疫荧光进一步表征了CD4+CD26-/lo-Teff细胞亚群。
结果：聚类分析根据临床和流式细胞数据将受试者分为四组，其中两组具有相反的炎症表型（即中性粒细胞型与嗜酸性粒细胞型）。中性粒细胞型哮喘表现为CD4-CD26hi细胞减少，与全身炎症呈负相关。嗜酸性粒细胞型哮喘表现为CD26-/lo亚群普遍增多。具体而言，哮喘患者中CD4+CD26-/lo-Teff增多，尤其是在过敏患者中，该亚群蛋白质组学特征为TEM/TEMA，表明固有蛋白（如MPO和RNASE2）和细胞骨架/细胞外基质（如MMP9和ACTN1）蛋白水平上调。免疫荧光检测证实CD4+T细胞存在非典型蛋白，且与CD4+T淋巴细胞相比，CD4+CD26-/lo-Teff中的“花状”核和MMP9/RNASE2水平富集。
结论：不同淋巴细胞亚群中的CD26表达水平与哮喘表型/严重程度相关。表达嗜酸性粒细胞/中性粒细胞特异性固有蛋白的CD4+CD26-/loTEMRA细胞可能是维持成人过敏性哮喘长期炎症的决定因素。
(中日友好医院呼吸与危重症医学科 张婧媛 摘译 林江涛 审校)
(Allergy. 2024 Sep 25. doi: 10.1111/all.16327. Epub ahead of print. PMID: 39319599.)
(Allergy. 2024 Sep 25. doi: 10.1111/all.16327. Epub ahead of print. PMID: 39319599.)
Exploring CD26-/lo subpopulations of lymphocytes in asthma phenotype and severity: A novel CD4+ T cell subset expressing archetypical granulocyte proteins.
Vázquez-Mera S, Martelo-Vidal L, Miguéns-Suárez P, Bravo SB, Saavedra-Nieves P, Arias P, Ferreiro-Posse A, Vázquez-Lago J, Salgado FJ, González-Barcala FJ, Nieto-Fontarigo JJ.
Abstract
BACKGROUND:Asthma pathology may induce changes in naïve/memory lymphocyte proportions assessable through the evaluation of surface CD26 (dipeptidyl peptidase 4/DPP4) levels.
OBJECTIVE:Our aim was to investigate the association of asthma phenotype/severity with the relative frequency of CD26-/lo, CD26int and CD26hi subsets within different lymphocyte populations.
METHODS:The proportion of CD26-/lo, CD26int and CD26hi subsets within CD4+ effector T cells (Teff), total CD4- lymphocytes, γδ-T cells, NK cells and NKT cells was measured in peripheral blood samples from healthy (N = 30) and asthma (N = 119) donors with different phenotypes/severities by flow cytometry. We performed K-means clustering analysis and further characterised the CD4+CD26-/lo Teff cell subset by LC-MS/MS and immunofluorescence.
RESULTS:Cluster analysis including clinical and flow cytometry data resulted in four groups, two of them with opposite inflammatory profiles (neutrophilic vs. eosinophilic). Neutrophilic asthma presented reduced CD4-CD26hi cells, which negatively correlated with systemic inflammation. Eosinophilic asthma displayed a general expansion of CD26-/lo subsets. Specifically, CD4+CD26-/lo Teff expansion was confirmed in asthma, especially in atopic patients. Proteomic characterisation of this subset with a TEM/TEMRA phenotype revealed upregulated levels of innate (e.g. MPO and RNASE2) and cytoskeleton/extracellular matrix (e.g. MMP9 and ACTN1) proteins. Immunofluorescence assays confirmed the presence of atypical proteins for CD4+ T cells, and an enrichment in 'flower-like' nuclei and MMP9/RNASE2 levels in CD4+CD26-/lo Teff compared to CD4+ T lymphocytes.
CONCLUSION: There is an association between CD26 levels in different lymphocyte subsets and asthma phenotype/severity. CD4+CD26-/lo TEMRA cells expressing innate proteins specific to eosinophils/neutrophils could be determinant in sustaining long-term inflammation in adult allergic asthma.
上一篇：
β-葡聚糖纳米颗粒可通过抑制小鼠铁死亡及DNA损伤缓解哮喘急性发作
下一篇：
重症哮喘微生物免疫相互作用的物种水平、宏基因组和蛋白质组学分析
