The Intersection between Immune System and Idiopathic Pulmonary Fibrosis—A Concise Review

Abstract

Idiopathic pulmonary fibrosis (IPF) is marked by progressive alveolar destruction, impaired tissue regeneration, and relentless fibrogenesis, culminating in respiratory failure and death. A diverse array of resident and non-resident cells within the lung contribute to disease pathogenesis. Notably, immune cells, both resident and recruited, respond to cues from sites of lung injury by undergoing phenotypic transitions and producing a wide range of mediators that influence, initiate, or dictate the function, or dysfunction, of key effector cells in IPF pathology, such as alveolar epithelial cells, lung fibroblasts, and capillary endothelial cells. The role of the immune system in IPF has undergone an interesting evolution, oscillating from initial enthusiasm to skepticism, and now to a renewed focus. This shift reflects both the past failures of immune-targeting therapies for IPF and the unprecedented insights into immune cell heterogeneity provided by emerging technologies. In this article, we review the historical evolution of perspectives on the immune system’s role in IPF pathogenesis and examine the lessons learned from previous therapeutic failures targeting immune responses. We discuss the major immune cell types implicated in IPF progression, highlighting their phenotypic transitions and mechanisms of action. Finally, we identify key knowledge gaps and propose future directions for research on the immune system in IPF.

Keywords

IPF / Macrophage / Innate immunity / Adaptive immunity / Clinical trial

Author Contributions

Conceptualization and Methodology: G.L., H.L., H.C.; Data Curation and Writing: H.L.; Review and Editing of this manuscript: G.L., H.L., H.C.

Ethics Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Funding

This work was supported by NIH grants R35HL135830 and R01AI170913 to G.L. and United States Department of Defense grant W81XWH-20-1-0226 to G.L.

Declaration of Competing Interest

The authors declare no competing interests.

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