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

ABSTRACT: Different naïve or memory cell subpopulations (i.e., central memory/CM, effector memory/EM, or terminally differentiated effector memory/EMRA) are involved in asthma development, and they display variable levels of the CD26 (dipeptidyl peptidase 4/DPP4). The phenotype and/or severity of the disease could drive to a phenotypic shift in naïve/memory lymphocyte subsets. Therefore, the aim of our work was to evaluate the association of the phenotype and severity of asthma with the relative frequency of CD26-/lo, CD26int, and CD26hi subsets within CD4+ effector T cells (Teff), total CD4- lymphocytes, γδ-T cells, NK cells, and NKT cells. For that, flow cytometry analyses were performed in peripheral blood samples from healthy donors (N=30) and asthma patients (N=119) with different phenotypes/severities. To avoid a priori bias, we have performed a K-means clustering analysis including clinical and flow cytometry data, resulting in four groups, two of them with opposite inflammatory profiles (eosinophilic vs. neutrophilic). CD4-CD26hi cells were reduced in neutrophilic asthma, and negatively correlated with degree of systemic inflammation. Interestingly, the eosinophilic group displayed a general expansion of CD26-/lo lymphocyte subsets. The expansion of CD4+CD26-/lo Teff cells with a TEM/TEMRA phenotype was confirmed in asthma, especially in atopic patients. Further characterisation of this subset by LC MS/MS revealed upregulated levels of innate (e.g., MPO and RNASE2) and cytoskeleton/extracellular matrix (e.g., MMP9, ACTN1) proteins, which matches its terminally differentiated phenotype. Validation by immunofluorescence confirmed the presence of many of these proteins in CD4+ T cells, as well as an enrichment in “flower-like” nuclei and MMP9/RNASE2 levels in CD4+CD26-/lo Teff compared to CD4+ T lymphocytes. Therefore, there is an association between CD26 levels in different lymphocyte subsets and asthma phenotypes/severities. CD4+CD26-/loTEMRA cells expressing innate proteins specific to eosinophils/neutrophils could be relevant in sustaining long-term inflammation in adult allergic asthma.

INSTRUMENT(S): TripleTOF 6600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Blood

SUBMITTER: Susana Bravo  

LAB HEAD: Suana Bravo

PROVIDER: PXD051222 | Pride | 2025-02-17

REPOSITORIES: pride