Profiles of circulating T follicular helper (cTfh) cell subpopulations in patients with asthma, COPD and asthma-COPD overlap (ACO)

Respir Med. 2026 Mar:253:108672. doi: 10.1016/j.rmed.2026.108672. Epub 2026 Jan 30.

Abstract

Background: Asthma, chronic obstructive pulmonary disease (COPD) and asthma-COPD Overlap (ACO) are inflammatory diseases characterized by specific T helper (Th) phenotypes. CD4 T follicular helper (Tfh) cells constitute a heterogeneous subset of T cells (Tfh1, Tfh2, Tfh17, Tfh17.1 and Tfr) essential for B cell differentiation and immunoglobulin production. Although alterations in their distribution and/or function have been associated with several pathologies, little is known about their relevance in these airway diseases.

Methods: We sought to evaluate, by flow cytometry, the pattern of blood follicular and non-follicular Th cell subpopulations in patients with asthma, COPD and ACO.

Results: We found a distinct and characteristic T cell pattern in these three inflammatory conditions: a predominance of cTfh2 in asthma patients, a Th17.1 and cTfh17.1 inflammatory profile in COPD patients, and a Th1 pattern in ACO patients. Regarding tobacco smoke, COPD patients who were active smokers had a higher ratio Th1/Th17 compared to ex-smokers with COPD, a trend not observed in ACO patients.

Conclusions: These results suggest that the assessment of the characteristic inflammatory profile for each of these pathologies could help to understand the pathobiology and to identify the most appropriate therapeutic target.

Keywords: ACO; Asthma; COPD; Circulating T follicular helper (cTfh); T helper (Th).

MeSH terms

  • Adult
  • Aged
  • Asthma* / blood
  • Asthma* / immunology
  • Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome* / blood
  • Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome* / immunology
  • Female
  • Flow Cytometry
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive* / blood
  • Pulmonary Disease, Chronic Obstructive* / immunology
  • Smoking / immunology
  • T Follicular Helper Cells* / immunology
  • T-Lymphocytes, Helper-Inducer* / immunology
  • Th17 Cells / immunology