Department of Biochemistry and Molecular Biology, Faculty of Biology-Biological Research Centre (CIBUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
Department of Medicine-University of Santiago de Compostela, Spanish Biomedical Research Networking Centre-CIBERES, Department of Respiratory Medicine-University Hospital of Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS.
J Investig Allergol Clin Immunol. 2018;28(2):113-125. doi: 10.18176/jiaci.0224. Epub 2018 Jan 3.
The pathogenesis of asthma is dependent on the balance between regulatory and effector T cells, which display differential expression of CD25 and CD26. Therefore, alteration of circulating levels of sCD25 and sCD26 during allergic asthma could be conditioned by changes in leukocyte phenotype. Objectives: To analyze expression of CD25 and CD26 on T lymphocytes and their soluble derivatives (sCD25, sCD26) during stable phases of moderate-severe allergic asthma.
Cross-sectional study with 2 adult cohorts of allergic asthmatics. Clinical, anthropometric, pulmonary, hematological, and biochemical parameters were measured. Phenotyping was performed with flow cytometry in both circulating and cultured leukocytes. Dipeptidyl peptidase 4 (DPP4) activity was assayed in culture supernatants.
In vitro studies revealed upregulation of CD26 on human T lymphocytes upon activation, especially under TH17-favoring conditions, and a correlation with soluble DPP4 activity (rs=0.641; P<.001). CD26 expression on lymphocytes was higher in asthmatics, while serum sCD26 was lower in women and patients. The latter finding could be associated with an expanded CD25low/CD26low/CD127low subset of effector CD4+ T cells in allergic asthma, with no changes in Treg percentages. However, women showed an increased Teff/Treg ratio, which could explain their greater susceptibility to asthma.
Allergic asthma causes an increment in CD25lowCD26low helper T cells detected in stable stages. These changes are mirrored in serum and should be considered in the light of the downmodulating role of CD26 in major chemokines related to the pathogenesis of asthma such as CCL11 (eotaxin), CCL5 (RANTES), and CXCL12a (SDF-1α).
哮喘的发病机制依赖于调节性和效应性 T 细胞之间的平衡，这些细胞表现出 CD25 和 CD26 的不同表达。因此，过敏性哮喘期间循环 sCD25 和 sCD26 水平的变化可能受到白细胞表型变化的影响。目的：分析中重度过敏性哮喘稳定期 T 淋巴细胞及其可溶性衍生物（sCD25、sCD26）上 CD25 和 CD26 的表达。
对 2 组成人过敏性哮喘患者进行横断面研究。测量临床、人体测量学、肺、血液和生化参数。使用流式细胞术对循环和培养的白细胞进行表型分析。在培养上清液中测定二肽基肽酶 4（DPP4）活性。
体外研究显示，人类 T 淋巴细胞在激活后 CD26 上调，尤其是在 TH17 倾向条件下，与可溶性 DPP4 活性呈正相关（rs=0.641；P<.001）。哮喘患者淋巴细胞上 CD26 的表达较高，而女性和患者的血清 sCD26 较低。这一发现可能与过敏性哮喘中效应性 CD4+T 细胞中 CD25low/CD26low/CD127low 亚群的扩张有关，而 Treg 百分比没有变化。然而，女性显示出效应 T 细胞/Treg 细胞比值增加，这可以解释她们对哮喘的易感性增加。
过敏性哮喘在稳定期引起 CD25lowCD26low 辅助性 T 细胞的增加。这些变化在血清中得到反映，应考虑到 CD26 在与哮喘发病机制相关的主要趋化因子（如 CCL11（嗜酸性粒细胞趋化因子）、CCL5（RANTES）和 CXCL12a（SDF-1α））中的下调作用。
