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Review
. 2021 Jan 5:13:1305-1318.
doi: 10.2147/JIR.S280958. eCollection 2020.

Genetic Risk Factors for Idiopathic Pulmonary Fibrosis: Insights into Immunopathogenesis

Jacob E Michalski  1 , David A Schwartz  1
Affiliations
Review

Genetic Risk Factors for Idiopathic Pulmonary Fibrosis: Insights into Immunopathogenesis

Jacob E Michalski et al. J Inflamm Res. .

Abstract

Idiopathic pulmonary fibrosis is an etiologically complex interstitial lung disease characterized by progressive scarring of the lungs with a subsequent decline in lung function. While much of the pathogenesis of IPF still remains unclear, it is now understood that genetic variation accounts for at least one-third of the risk of developing the disease. The single-most validated and most significant risk factor, genetic or otherwise, is a gain-of-function promoter variant in the MUC5B gene. While the functional impact of these IPF risk variants at the cellular and tissue levels are areas of active investigation, there is a growing body of evidence that these genetic variants may influence disease pathogenesis through modulation of innate immune processes.

Keywords: MUC5B; genetics; host defense; innate immunity; interstitial lung disease; pulmonary fibrosis.

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Conflict of interest statement

Dr David A Schwartz reports grants from NIH-NHLBI (UG3/UH3-HL151865), DoD Focused Program Project (W81XWH-17-1-0597), NIH-NHLBI (R01-HL149836), VAMC Merit Review (IO1BX005295), NIH-NHLBI (P01-HL0928701), NIH-NHLBI (UH2/3-HL123442), and NIH-NHLBI (X01-HL134585), during the conduct of the study; personal fees from Eleven P15, Inc. (a company with the mission of early detection and early intervention of IPF), outside the submitted work; In addition, Dr David A Schwartz has patents 14/813.559, 62/624500 pending, and a patent 8,673,565 issued. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Innate immune and host defense mechanisms in the distal airway and alveolus are multi-tiered.
Figure 2
Figure 2
Genetic variants disrupt TLR/IL-1R family signaling in IPF.
Figure 3
Figure 3
Genetic-driven innate immunity changes contribute to IPF pathogenesis.
See this image and copyright information in PMC

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