Expansion of a CD26low Effector TH Subset and Reduction in Circulating Levels of sCD26 in Stable Allergic Asthma in Adults
Nieto-Fontarigo JJ1, González-Barcala FJ2, San-José ME3, Cruz MJ4, Linares T5, Soto-Mera MT5, Valdés-Cuadrado L6, García-González MA7, Andrade-Bulos LJ1, Arias P1, Nogueira M1, Salgado FJ1
1Department of Biochemistry and Molecular Biology, Faculty of Biology-Biological Research Centre (CIBUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain
2Department 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)
3Clinical Analysis Service, USC University Hospital Complex (CHUS), Santiago de Compostela, Spain
4Department of Respiratory Medicine-Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. Spanish Biomedical Research Networking Centre-CIBERES
5Allergy Department, University Hospital of Pontevedra (CHOP), Pontevedra, Spain
6Department of Medicine-University of Santiago de Compostela, Department of Respiratory Medicine-University Hospital of Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS)
7Laboratory of Nephrology, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
J Investig Allergol Clin Immunol 2018; Vol 28(2)
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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).
Key words: Asthma biomarkers, CD25, CD26, DPP4, Lymphocytes, Helper T cells