Enhanced CCL2–CCR2 signalling promotes recruitment of monocyte-derived macrophages in progressive fibrosing hypersensitivity pneumonitis
Year: 2026
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Hypersensitivity pneumonitis is characterized by immune dysregulation that often leads to irreversible lung tissue scarring. While elevated monocytes play a key role in idiopathic pulmonary fibrosis, their contribution in progressive fibrotic hypersensitivity pneumonitis, along with the role of the CCL2 chemoattractant, requires clarification. METHODS: Immune characterization of circulating and lung markers of 71 patients with fibrotic hypersensitivity pneumonitis with median follow-up time of 35.8 months (57.7% progressed, 31% exacerbated), comparing with controls, non-fibrotic cases and idiopathic pulmonary fibrosis. RESULTS: Elevated serum CCL2 strongly associated with disease progression and acute exacerbations, with baseline levels above 1080 pg/mL predicting progression and shorter survival. Despite significant variability in CCL2 levels over time, their elevation near progression was consistent, suggesting a role for this chemokine in the fibrotic cascade. Moreover, classical monocytes from patients with progressive disease displayed higher CCR2 expression, and peripheral blood mononuclear cells from these patients showed enhanced CCL2-driven chemotaxis. Bronchoalveolar lavage immunophenotyping identified enriched CCR2 + monocyte-derived precursors in fibrotic hypersensitivity pneumonitis, implicating this cellular population in disease severity. Genetic analysis of CCL2/CCR2 revealed no association between their expression and known polymorphisms. Mechanistically, elevated CCL2 may drive disease progression by recruiting CCR2 + monocytes, contributing to the profibrotic microenvironment. CONCLUSIONS: These findings underscore the CCL2/CCR2 axis as a promising biomarker pathway for disease monitoring in fibrotic hypersensitivity pneumonitis, which could guide therapeutic interventions and stratification of high-risk patients.
Source: Respiratory Research
Authors: Rita F. Santos, Catarina Gouveia Cardoso, Ana Pinto, Luciana Oliveira, David Barros Coelho, Melany Gonçalves, André Terras Alexandre, Natália Melo, Patrícia Caetano Mota, Inês Neves, Verónica Cardoso, Susana Guimarães, Conceição Souto Moura, André Carvalho, Luís Flores, Fernando Friões, Pedro Fernandes, Andreia Coelho, Oksana Sokhatska, Marília Beltrão, Luís Delgado, Francisco Vasques-Nóvoa, Adelino Leite Moreira, António Morais, Margarida Saraiva, Helder Novais Bastos
Institutions: i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Universidade Técnica do Porto, Universidade do Porto, Hospital de São João, RISE - Health Research Network, Unidade Local de Saúde de Matosinhos, Unidade Local de Saúde do Tâmega e Sousa, Instituto de Biologia Molecular e Celular
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,490
OpenAlex ID: W7153190542