Immune Mechanisms in Pulmonary Fibrosis

Abstract

Pulmonary fibrosis, particularly idiopathic pulmonary fibrosis, represents a chronic and progressive disease with high mortality and limited therapeutic options. Excessive deposition of extracellular matrix proteins results in fibrotic remodeling, alveolar destruction, and irreversible loss of lung function. Both innate and adaptive immune mechanisms contribute to fibrogenesis at several cellular and noncellular levels. Here, we summarize and discuss the role of immune cells (T cells, neutrophils, macrophages, and fibrocytes) and soluble mediators (cytokines and chemokines) involved in pulmonary fibrosis, pointing toward novel immune-based therapeutic strategies in the field.

Cannabinoid CB1 receptor overactivity contributes to the pathogenesis of idiopathic pulmonary fibrosis

“…This suggests that the Tgfβ1 pathway may be a dominant target of CB 1 R-mediated fibrogenesis in PF. The alveolar macrophages are a known source of Tgfβ1 that contributes to the profibrogenic milieu in the lung (63). In contrast to the preferential activation of fibrogenic gene expression by CB 1 R over iNOS in the lungs of bleomycin-treated mice, iNOS activity was not significantly affected by Cnr1 deletion, whereas it was absent in the Nos2 -/-mice (Figure 7), suggesting corresponding differences in the degree of nitrosative stress.…”

Innate Immunity of the Lung: From Basic Mechanisms to Translational Medicine

“…Overall, the complex multifunctionality of AM, interacting as antigen-presenting cells with T cells, clearing apoptotic and necrotic cells through efferocytosis, and killing pathogens and releasing both pro- and anti-inflammatory factors, makes a “good-versus-bad-cop” assignment for these cells for the majority of lung diseases challenging. In vivo macrophage depletion studies revealed different outcomes depending on the lung disease model and the time point of intervention used [64, 65, 79, 80]. Idiopathic pulmonary fibrosis (IPF) is a prototypic example of a complex chronic lung disease in which the role of pulmonary macrophages remains controversial.…”

“…In this context, AM seem to play a dual role in lung fibrosis given their release of profibrotic factors (such as TGF-β 1 and PDGF), thereby driving disease progression and, on the other hand, their ability to release proteases (MMP) that can digest the extracellular matrix and thus exert antifibrotic/fibrinolytic activities. For a more thorough discussion of macrophage phenotypes and functions in IPF, we refer readers to a recent review in that field [79]. …”

Interstitial Pneumonia Associated with Connective Tissue Disease: An Overview and an Insight

“…Besides, as concerns idiopathic pulmonary fibrosis (IPF), the latest evidence of immune mechanisms in IPF was reviewed in the recent literature, which includes involvement of both innate immunity and adaptive immunity at several levels of the processes toward development of fibrinogenesis in the human lung of IPF or in its model mice, as summarized in Table 5 [158]. Briefly, in adaptive immune system, the role of T cells seems complex and subset dependent; Th2 and Th17 cells were shown to promote pulmonary fibrosis, although Th1, Th22, and γδ-T cells have been found to attenuate fibrotic disease.…”

“…Treg and Th9 subsets have been proposed to exert both anti-and profibrotic effects. In innate immunity, M2 macrophages and neutrophils have been suggested to enhance pulmonary fibrosis, whereas M1 macrophages were assigned a protective role, but contradictory findings have also been described [158].…”