Pulmonary 5-HT2B receptor expression in fibrotic interstitial lung diseases

Pulmonary fibrosis is a severe condition in interstitial lung diseases (ILD) such as idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-ILD, where the underlying mechanism is not well defined and with no curative treatments available. Serotonin (5-HT) signaling via the 5-HT_2B receptor has been recognized as a promising preclinical target for fibrosis. Despite this, the involvement of the 5-HT_2B receptor in fibrotic ILD is widely unexplored. This work highlights the spatial pulmonary distribution of the 5-HT_2B receptor in patients with IPF and systemic sclerosis-ILD. We show that the 5-HT_2B receptor is located in typical pathological structures e.g. honeycomb cysts and weakly in fibroblast foci. Together with immunohistochemistry and immunofluorescence stainings of patient derived distal lung tissues, we identified cell targets for 5-HT_2B receptor interference in type II alveolar epithelial cells, endothelial cells and M2 macrophages. Our results emphasize the role of 5-HT_2B receptor as a target in lung fibrosis, warranting further consideration in targeting fibrotic ILDs.