Department of Biochemistry and Molecular Biology, Faculty of Biology-Biological Research Centre (CIBUS), University of Santiago de Compostela (USC), Santiago de Compostela, Spain.
Respiratory Department, Clinic University Hospital (CHUS), Santiago de Compostela, Spain.
Clin Rev Allergy Immunol. 2019 Apr;56(2):139-160. doi: 10.1007/s12016-016-8578-z.
Asthma is a heterogeneous and chronic inflammatory family of disorders of the airways with increasing prevalence that results in recurrent and reversible bronchial obstruction and expiratory airflow limitation. These diseases arise from the interaction between environmental and genetic factors, which collaborate to cause increased susceptibility and severity. Many asthma susceptibility genes are linked to the immune system or encode enzymes like metalloproteases (e.g., ADAM-33) or serine proteases. The S9 family of serine proteases (prolyl oligopeptidases) is capable to process peptide bonds adjacent to proline, a kind of cleavage-resistant peptide bonds present in many growth factors, chemokines or cytokines that are important for asthma. Curiously, two serine proteases within the S9 family encoded by genes located on chromosome 2 appear to have a role in asthma: CD26/dipeptidyl peptidase 4 (DPP4) and DPP10. The aim of this review is to summarize the current knowledge about CD26 and to provide a structured overview of the numerous functions and implications that this versatile enzyme could have in this disease, especially after the detection of some secondary effects (e.g., viral nasopharyngitis) in type II diabetes mellitus patients (a subset with a certain risk of developing obesity-related asthma) upon CD26 inhibitory therapy.
哮喘是一种异质性和慢性炎症性气道疾病家族，其患病率不断增加，导致反复发生和可逆性支气管阻塞以及呼气气流受限。这些疾病是由环境和遗传因素相互作用引起的，这些因素共同导致易感性和严重程度增加。许多哮喘易感性基因与免疫系统有关，或编码金属蛋白酶（如 ADAM-33）或丝氨酸蛋白酶。丝氨酸蛋白酶 S9 家族（脯氨酰寡肽酶）能够在靠近脯氨酸的肽键处进行加工，脯氨酸是许多生长因子、趋化因子或细胞因子中存在的一种不易断裂的肽键，这些物质对哮喘很重要。奇怪的是，位于 2 号染色体上的基因编码的 S9 家族中的两种丝氨酸蛋白酶似乎在哮喘中发挥作用：CD26/二肽基肽酶 4 (DPP4) 和 DPP10。本综述的目的是总结目前关于 CD26 的知识，并提供该多功能酶在该疾病中可能具有的众多功能和影响的结构化概述，特别是在检测到某些继发效应（例如，II 型糖尿病患者的病毒性鼻咽部炎症）之后）在 CD26 抑制治疗后（具有发展为肥胖相关哮喘一定风险的亚组）。
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