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Review
. 2024 Jul 10;25(14):7554.
doi: 10.3390/ijms25147554.

Exploring the Interplay between Cellular Senescence, Immunity, and Fibrosing Interstitial Lung Diseases: Challenges and Opportunities

Fernanda Hernandez-Gonzalez  1   2   3 , Federico Pietrocola  4 , Paolo Cameli  5 , Elena Bargagli  5 , Sergio Prieto-González  2   3   6 , Tamara Cruz  2   7 , Nuria Mendoza  2   3   7 , Mauricio Rojas  8 , Manuel Serrano  9 , Alvar Agustí  1   2   3   7 , Rosa Faner  2   7   10 , Jose A Gómez-Puerta  2   11 , Jacobo Sellares  1   2   3   7
Affiliations
Review

Exploring the Interplay between Cellular Senescence, Immunity, and Fibrosing Interstitial Lung Diseases: Challenges and Opportunities

Fernanda Hernandez-Gonzalez et al. Int J Mol Sci. .

Abstract

Fibrosing interstitial lung diseases (ILDs) are characterized by the gradual and irreversible accumulation of scar tissue in the lung parenchyma. The role of the immune response in the pathogenesis of pulmonary fibrosis remains unclear. In recent years, substantial advancements have been made in our comprehension of the pathobiology driving fibrosing ILDs, particularly concerning various age-related cellular disturbances and immune mechanisms believed to contribute to an inadequate response to stress and increased susceptibility to lung fibrosis. Emerging studies emphasize cellular senescence as a key mechanism implicated in the pathobiology of age-related diseases, including pulmonary fibrosis. Cellular senescence, marked by antagonistic pleiotropy, and the complex interplay with immunity, are pivotal in comprehending many aspects of lung fibrosis. Here, we review progress in novel concepts in cellular senescence, its association with the dysregulation of the immune response, and the evidence underlining its detrimental role in fibrosing ILDs.

Keywords: cellular senescence; immunosenescence; lung fibrosis.

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Conflict of interest statement

F.H.-G. and J.S. report honoraria for lectures, educational events, and support for attending meetings from Roche, Boehringer Ingelheim, AstraZeneca, Gebro, and GSK, outside the submitted work. J.S. discloses consulting fees from Boehringer Ingelheim and Alofarma, and grants from Roche and Boehringer Ingelheim, all outside the submitted work. P.C. reports honoraria for lectures, educational events, and support for attending meetings from AstraZeneca, GSK, Sanofi and Chiesi, outside the submitted work. R.F. reports honoraria for lectures and support for attending meetings from Chiesi and Zambon; grants from GSK, AstraZeneca, and Menarini; and consulting fees from GSK, all outside the submitted work. M.S. is shareholder of Altos Labs, Inc., Senolytic Therapeutics, Inc., Life Biosciences, Inc., and Rejuveron Senescence Therapeutics, AG. J.A.G-P. reports honoraria for lectures, educational events, and support for attending meetings from AbbVie, AstraZeneca, Boehringer Ingelheim, GSK, Galapagos, Janssen, Lilly, and Otsuka, outside the submitted work. The funders had no role in the writing of the manuscript. The remaining authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Overview of the hallmarks of aging, lung fibrosis, and their similarities with the main pathways of immunosenescence. The diagram illustrates the points of overlap between the hallmarks of aging (on the right) and lung fibrosis (on the left), suggesting that many of these factors likely contribute to immunosenescence and lung fibrosis.
Figure 2
Figure 2
Crosstalk between senescent and immune cells in fibrosing interstitial lung diseases. The biological disturbances in senescent cells enable them to engage in complex communication with the host immune system. Various immune cell populations actively participate in the surveillance and regulation of these senescent cells, highlighting the intricate interplay between cellular senescence and immune responses in pulmonary fibrosis. NK: Natural Killer; NKG2: natural killer group 2; MICA: MHC class I polypeptide-related sequence; HLA-E: Major Histocompatibility Complex; Class I, E, CALR: Calreticulin; CD47: Cluster of Differentiation 47; CD24: Cluster of Differentiation 24. Figure created using BioRender (https://biorender.com), accessed on 7 July 2024.
Figure 3
Figure 3
Senolytic strategies with emerging evidence in pulmonary fibrosis. This figure presents a compilation of senolytic treatments validated in lung fibrosis, detailing their mechanisms of action and biological effects. Those highlighted in blue are recognized for their potential to modulate immune pathways [124,125,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143].
See this image and copyright information in PMC

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