Exploring CD26 -/lo subpopulations of lymphocytes in asthma phenotype and severity: A novel CD4 + T cell subset expressing archetypical granulocyte proteins.

Autor: Vázquez-Mera S; Department of Biochemistry and Molecular Biology, Faculty of Biology-Biological Research Centre (CIBUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.; Translational Research In Airway Diseases Group (TRIAD), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain., Martelo-Vidal L; Department of Biochemistry and Molecular Biology, Faculty of Biology-Biological Research Centre (CIBUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.; Translational Research In Airway Diseases Group (TRIAD), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain., Miguéns-Suárez P; Department of Biochemistry and Molecular Biology, Faculty of Biology-Biological Research Centre (CIBUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.; Translational Research In Airway Diseases Group (TRIAD), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain., Bravo SB; Proteomic Unit, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, Spain., Saavedra-Nieves P; Department of Statistics, Mathematical Analysis and Optimization, Universidade de Santiago de Compostela, Santiago de Compostela, Spain., Arias P; Department of Biochemistry and Molecular Biology, Faculty of Biology-Biological Research Centre (CIBUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.; Translational Research In Airway Diseases Group (TRIAD), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain., Ferreiro-Posse A; Department of Respiratory Medicine, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain., Vázquez-Lago J; Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela, Spain., Salgado FJ; Department of Biochemistry and Molecular Biology, Faculty of Biology-Biological Research Centre (CIBUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.; Translational Research In Airway Diseases Group (TRIAD), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain., González-Barcala FJ; Translational Research In Airway Diseases Group (TRIAD), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain.; Department of Respiratory Medicine, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain.; Department of Medicine, Universidade de Santiago de Compostela, Santiago de Compostela, Spain., Nieto-Fontarigo JJ; Department of Biochemistry and Molecular Biology, Faculty of Biology-Biological Research Centre (CIBUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.; Translational Research In Airway Diseases Group (TRIAD), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain.
Jazyk: angličtina
Zdroj: Allergy [Allergy] 2024 Nov; Vol. 79 (11), pp. 3005-3021. Date of Electronic Publication: 2024 Sep 25.
DOI: 10.1111/all.16327
Abstrakt: Background: Asthma pathology may induce changes in naïve/memory lymphocyte proportions assessable through the evaluation of surface CD26 (dipeptidyl peptidase 4/DPP4) levels. Our aim was to investigate the association of asthma phenotype/severity with the relative frequency of CD26 -/lo , CD26 int and CD26 hi subsets within different lymphocyte populations.
Methods: The proportion of CD26 -/lo , CD26 int and CD26 hi subsets within CD4 + effector T cells (T eff ), 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 T eff 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 - CD26 hi cells, which negatively correlated with systemic inflammation. Eosinophilic asthma displayed a general expansion of CD26 -/lo subsets. Specifically, CD4 + CD26 -/lo T eff expansion was confirmed in asthma, especially in atopic patients. Proteomic characterisation of this subset with a T EM /T EMRA 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 T eff compared to CD4 + T lymphocytes.
Conclusion: There is an association between CD26 levels in different lymphocyte subsets and asthma phenotype/severity. CD4 + CD26 -/lo T EMRA cells expressing innate proteins specific to eosinophils/neutrophils could be determinant in sustaining long-term inflammation in adult allergic asthma.
(© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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