Immune-neural cell crosstalk in chronic lung disease (fibrosis)

Project Description: Respiratory diseases present a health challenge that spans the globe and accounts for one-tenth of all disability adjusted life years lost globally. Pulmonary fibrosis (PF) is chronic progressive disease and a leading cause of the need for lung transplantation. PF results from a dysregulation of repair events after environmentally driven damage. The role of inflammatory responses following pulmonary damage have been extensively studied, there is very little known about the contribution of non-immune cells to respiratory disease. Neuroimmune interactions are increasing recognised to control inflammation but pulmonary neuronal networks have historically been difficult to study. Preliminary data and tools: Preliminary analysis of human lung fibrosis revealed increased numbers of neuropeptide (CGRP) producing neuroendrocrine cells in the lung epithelium (PNECs) and this was confirmed in murine models of PF. Light sheet microscopy of murine lungs further revealed an increase in the length and branching of pulmonary neurons in PF. This project utilises immunohistochemistry, 3D imaging of cleared tissues, scRNAseq and immune cell assays together with diease modelling in transgenic reporter and gene deficient mice to ascertain the contribution of PNECs and nociceptor neurons to lung fibrosis and to assess the therapeutic potential of targeting the major neurotransimitters (such as CGRP) utilised by these cells to communicate with the immune system.