Immune mechanisms in fibrotic interstitial lung disease

• Published in: Cell Vol. 187; no. 14; pp. 3506 - 3530
• Main Authors: Kamiya, Mari, Carter, Hannah, Espindola, Milena S., Doyle, Tracy J., Lee, Joyce S., Merriam, Louis T., Zhang, Fan, Kawano-Dourado, Leticia, Sparks, Jeffrey A., Hogaboam, Cory M., Moore, Bethany B., Oldham, William M., Kim, Edy Y.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.07.2024
• Subjects: Adaptive Immunity; Animals; fibroblasts; Humans; idiopathic pulmonary fibrosis; immune system; Immunity, Innate; Immunotherapy; interstitial lung diseases; Lung - immunology; Lung - pathology; Lung Diseases, Interstitial - immunology; Lung Diseases, Interstitial - pathology; pulmonary fibrosis; Pulmonary Fibrosis - immunology; Pulmonary Fibrosis - pathology; immune system; fibroblasts; idiopathic pulmonary fibrosis; interstitial lung diseases; pulmonary fibrosis
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2024.05.015

Fibrotic interstitial lung diseases (fILDs) have poor survival rates and lack effective therapies. Despite evidence for immune mechanisms in lung fibrosis, immunotherapies have been unsuccessful for major types of fILD. Here, we review immunological mechanisms in lung fibrosis that have the potential to impact clinical practice. We first examine innate immunity, which is broadly involved across fILD subtypes. We illustrate how innate immunity in fILD involves a complex interplay of multiple cell subpopulations and molecular pathways. We then review the growing evidence for adaptive immunity in lung fibrosis to provoke a re-examination of its role in clinical fILD. We close with future directions to address key knowledge gaps in fILD pathobiology: (1) longitudinal studies emphasizing early-stage clinical disease, (2) immune mechanisms of acute exacerbations, and (3) next-generation immunophenotyping integrating spatial, genetic, and single-cell approaches. Advances in these areas are essential for the future of precision medicine and immunotherapy in fILD. Fibrotic interstitial lung diseases have poor survival rates, with current immunotherapies proving ineffective. This review examines underlying innate and adaptive immune mechanisms and potential clinical impacts. It lays the groundwork for future studies on early disease stages, acute exacerbation mechanisms, and advanced immunophenotyping to enhance therapeutic outcomes.