Short-range interactions between fibrocytes and CD8⁺T cells in COPD bronchial inflammatory response

Abstract

The peri-bronchial zone of chronic obstructive pulmonary disease (COPD) is the site of extensive infiltration of immune cell, allowing persistent contacts between resident cells and immune cells. Tissue fibrocytes interaction with CD8+T cells and its consequences were investigated. We show that interactions beween both cell types are more frequent in distal airways from COPD patients compared to those of control subjects. Tissular CD8+T cells from COPD patients promote fibrocyte chemotaxis via the CXCL8-CXCR1/2 axis. CD8+T cells establish short-term interactions with fibrocytes, that trigger CD8+T cell proliferation in a CD54- and CD86-dependent manner, as well as pro-inflammatory cytokines production. A computational model accurately predicts histologicalex vivocharacteristics and allows to monitors disease evolution. Overall, our study reveals that local interactions between fibrocytes and CD8+T cells may comromise the balance between protective immunity and chronic inflammation in bronchi of COPD patients.TeaserFibrocytes/CD8+T cells interactions cause inflammation through a maintained pathophysiological loop in bronchi of COPD patients.

CXCR4 blockade alleviates pulmonary and cardiac outcomes in early COPD

“…These results are in agreement with findings obtained in mice treated with another CXCR4 antagonist or with CXCL12 neutralizing antibodies, in the context of pulmonary fibrosis, where reduction of fibrocytes accumulation concomitantly improved lung outcomes (13, 32). The reduction of tissue fibrocytes could thus contribute to lower chronic inflammation (33). Finally, plerixafor-induced increased mobilization of hematopoietic progenitor cells from the bone marrow may also participate in the improvement of lung function and remodeling as suggested by another study showing that plerixafor-treated mice were protected against CS-induced emphysema (12).…”

“…Additionally, and importantly, these fibrocytes could also perpetuate chronic inflammation, through interaction with CD8 + T cells. Such cells are indeed implicated in COPD lung pathogenesis (43) and we have recently shown that fibrocytes directly interact with CD8+ T cells in the lungs, leading to increased proliferation and activation (44).…”