Decreased expression of transmembrane TNFR2 in lung leukocytes subpopulations of patients with non-fibrotic hypersensitivity pneumonitis compared with the fibrotic disease

Abstract

Hypersensitivity pneumonitis (HP) is an interstitial lung disease, characterized by lung inflammation (non-fibrotic HP) that may often progresses to fibrosis (Fibrotic HP). The tumor necrosis factor (TNF) and its receptors (TNFR1 and TNFR2) can be found as soluble (sol) and transmembrane (tm) forms, playing pro-inflammatory functions but also has been related to immune regulatory functions. Bronchioalveolar lavage from fibrotic and non-fibrotic HP patients was obtained, and immune cells were characterized by flow cytometry, whereas soluble proteins were analyzed by ELISA. Compare to fibrotic HP patients, HP patients with non-fibrotic disease have accumulation of pro-inflammatory CD3+ myeloid cells, cell subpopulations that have decreased tmTNFR2 expression, and low frequency of regulatory-T cells. Whereas solTNF, solTNFR2, and IL-8 are increased. These findings suggest that the TNF pathway may explain, at least partially, the differences between both HP clinical forms. The evaluation of the TNF family molecules may help to develop new therapeutic approaches.