The Epithelial-Immune Crosstalk in Pulmonary Fibrosis

Abstract

Interactions between the lung epithelium and the immune system involve a tight regulation to prevent inappropriate reactions and have been connected to several pulmonary diseases. Although the distal lung epithelium and local immunity have been implicated in the pathogenesis and disease course of idiopathic pulmonary fibrosis (IPF), consequences of their abnormal interplay remain less well known. Recent data suggests a two-way process, as illustrated by the influence of epithelial-derived periplakin on the immune landscape or the effect of macrophage-derived IL-17B on epithelial cells. Additionally, damage associated molecular patterns (DAMPs), released by damaged or dying (epithelial) cells, are augmented in IPF. Next to “sterile inflammation”, pathogen-associated molecular patterns (PAMPs) are increased in IPF and have been linked with lung fibrosis, while outer membrane vesicles from bacteria are able to influence epithelial-macrophage crosstalk. Finally, the advent of high-throughput technologies such as microbiome-sequencing has allowed for the identification of a disease-specific microbial environment. In this review, we propose to discuss how the interplays between the altered distal airway and alveolar epithelium, the lung microbiome and immune cells may shape a pro-fibrotic environment. More specifically, it will highlight DAMPs-PAMPs pathways and the specificities of the IPF lung microbiome while discussing recent elements suggesting abnormal mucosal immunity in pulmonary fibrosis.

RNA Sequencing of Epithelial Cell/Fibroblastic Foci Sandwich in Idiopathic Pulmonary Fibrosis: New Insights on the Signaling Pathway

“…In vivo, experimental models have shown that several mucins (MUC1, MUC5b, MUC4) can influence EMT through different mechanisms, such as promoting fibroblast proliferation and migration while exerting also anti-apoptotic activities [ 52 , 53 , 54 , 55 ]. Indeed, their genetic and pharmacologic modulation was found to protect bleomycin-treated mice by interfering with TGF-β1-induced EMT or myofibroblast differentiation [ 56 ].…”

Optimization of Primary Human Bronchial Epithelial 3D Cell Culture with Donor-Matched Fibroblasts and Comparison of Two Different Culture Media

“…The respiratory epithelium plays a pivotal role in disease pathogenesis and progression [ 2 , 3 ]. In addition, for the treatment of lung diseases as well as other organ diseases, the respiratory epithelium, with its size of 100 square meters, represents a promising approach for drug delivery.…”

Effect of M6A regulators on diagnosis, subtype classification, prognosis and novel therapeutic target development of idiopathic pulmonary fibrosis

“…Activation of innate immunity, including monocyte, macrophage, dendritic cell and mast cell, is responsible for progression and a poor prognosis of IPF( Scott, Quinn et al, 2019 ; Overed-Sayer, Miranda et al, 2020 ; Bocchino, Zanotta et al, 2021 ; Mattoo and Pillai 2021 ; Shenderov, Collins et al, 2021 ; van Geffen, Deißler et al, 2021 ). Th1/Th2 imbalance also contributes to aggravation of IPF, but which of them plays a dominant role remains controversial ( Desai, Winkler et al, 2018 ; Planté-Bordeneuve, Pilette et al, 2021 ; Shenderov, Collins et al, 2021 ). Th17 cell and Treg cell have been proven positively associated with the development of IPF ( Shenderov, Collins et al, 2021 ; van Geffen, Deißler et al, 2021 ).…”