CCR6+ T cells as potential drivers of inflammation in chronic thromboembolic pulmonary hypertension

Introduction

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is one of the leading causes of severe hypertension, characterized by chronic fibrotic thrombi. Increasing evidence highlights a role for inflammation and immune dysregulation in the pathogenesis of CTEPH; however, it remains unclear whether systemic inflammation contributes directly to chronic thrombus formation and how it influences subsequent vascular remodeling. The aim of this study was to characterize peripheral blood T-lymphocyte subsets in patients with CTEPH

Methods

High-dimensional flow cytometry was employed to profile peripheral T lymphocytes in 23 patients with prevalent CTEPH and 15 age- and sex-matched healthy controls (HC) (Table 1). A total of 288 T-cell subpopulations were identified and analyzed based on detailed phenotypic and functional markers expression.

Results

The main findings in the CTEPH group demonstrated a significant reduction in total lymphocytes compared with HC, including CD4+ T cells, CD8+ T cells, CD4⁻CD8⁻ T cells, and follicular CD195⁻CD196⁻ subsets. Notably, an expansion of naïve CD4+ T-cell compartments was observed, whereas CD8+ T cells exhibited increased proportions of effector memory and effector subsets. Both CD4+ and CD8+ T cells showed a marked enrichment in the CCR6 phenotype.

Analysis of activation markers further revealed increased frequencies of CD8+CCR5+CCR6+ T cells, activated CD8+follicular T cells, and CD4+CD8+ activated T cells. Importantly, within the CD25+ population, a significant expansion of CCR6-expressing cells was detected in both CD4+ and CD8+ T-cell subsets. This pattern supports an ongoing inflammatory immune response.

Conclusion

These findings reveal a profound remodeling of the T-lymphocyte compartment in patients with CTEPH. We observed a redistribution of CD4+ and CD8+ memory subsets, together with enrichment of CCR6-expressing populations. CCR6 is a phenotypic marker of Th17/Tc17 cells, which are typically associated with IL-17 production and the promotion of chronic inflammatory responses. Collectively, these results support a potential role for CCR6+ T cell–driven immunopathology in CTEPH. Further studies are warranted to clarify the functional contribution of these cells and to explore whether therapeutic strategies targeting CCR6+ T cell pathways could represent a novel approach in CTEPH management.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.