Cytoplasmic DNAs: Sources, Sensing, and Roles in the Development of Lung Inflammatory Diseases and Cancer

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 May 1

PMID 37122745

Authors

Xintong He

Ye Sun

Jianzhang Lu

Faiza Naz

Shenglin Ma

Jian Liu

Affiliations

Soon will be listed here.

Abstract

Cytoplasmic DNA is emerging as a pivotal contributor to the pathogenesis of inflammatory diseases and cancer, such as COVID-19 and lung carcinoma. However, the complexity of various cytoplasmic DNA-related pathways and their crosstalk remains challenging to distinguish their specific roles in many distinct inflammatory diseases, especially for the underlying mechanisms. Here, we reviewed the latest findings on cytoplasmic DNA and its signaling pathways in inflammatory lung conditions and lung cancer progression. We found that sustained activation of cytoplasmic DNA sensing pathways contributes to the development of common lung diseases, which may result from external factors or mutations of key genes in the organism. We further discussed the interplays between cytoplasmic DNA and anti-inflammatory or anti-tumor effects for potential immunotherapy. In sum, this review aids in understanding the roles of cytoplasmic DNAs and exploring more therapeutic strategies.

Citing Articles

RNA sensing induced by chromosome missegregation augments anti-tumor immunity.

Sasaki N, Homme M, Murayama T, Osaki T, Tenma T, An T Mol Cell. 2024; 85(4):770-786.e7.

PMID: 39706184 PMC: 11888943. DOI: 10.1016/j.molcel.2024.11.025.

Immunotherapies for locally aggressive cancers.

Adams S, Nambiar A, Bressler E, Raut C, Colson Y, Wong W Adv Drug Deliv Rev. 2024; 210:115331.

PMID: 38729264 PMC: 11228555. DOI: 10.1016/j.addr.2024.115331.

Self-DNA driven inflammation in COVID-19 and after mRNA-based vaccination: lessons for non-COVID-19 pathologies.

Heil M Front Immunol. 2024; 14:1259879.

PMID: 38439942 PMC: 10910434. DOI: 10.3389/fimmu.2023.1259879.

References

Sui H, Chen Q, Imamichi T . Cytoplasmic-translocated Ku70 senses intracellular DNA and mediates interferon-lambda1 induction. Immunology. 2021; 163(3):323-337. PMC: 8207419. DOI: 10.1111/imm.13318. View

Wang Y, Fu Z, Li X, Liang Y, Pei S, Hao S . Cytoplasmic DNA sensing by KU complex in aged CD4 T cell potentiates T cell activation and aging-related autoimmune inflammation. Immunity. 2021; 54(4):632-647.e9. DOI: 10.1016/j.immuni.2021.02.003. View

Kinoshita T, Goto T . Molecular Mechanisms of Pulmonary Fibrogenesis and Its Progression to Lung Cancer: A Review. Int J Mol Sci. 2019; 20(6). PMC: 6471841. DOI: 10.3390/ijms20061461. View

Barton G, Kagan J, Medzhitov R . Intracellular localization of Toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA. Nat Immunol. 2005; 7(1):49-56. DOI: 10.1038/ni1280. View

Kumar V . The Trinity of cGAS, TLR9, and ALRs Guardians of the Cellular Galaxy Against Host-Derived Self-DNA. Front Immunol. 2021; 11:624597. PMC: 7905024. DOI: 10.3389/fimmu.2020.624597. View

Rivera Vargas T, Apetoh L . Danger signals: Chemotherapy enhancers?. Immunol Rev. 2017; 280(1):175-193. DOI: 10.1111/imr.12581. View

Gordon A, Mouncey P, Al-Beidh F, Rowan K, Nichol A, Arabi Y . Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19. N Engl J Med. 2021; 384(16):1491-1502. PMC: 7953461. DOI: 10.1056/NEJMoa2100433. View

Bennion B, Ingle H, Ai T, Miner C, Platt D, Smith A . A Human Gain-of-Function STING Mutation Causes Immunodeficiency and Gammaherpesvirus-Induced Pulmonary Fibrosis in Mice. J Virol. 2018; 93(4). PMC: 6364005. DOI: 10.1128/JVI.01806-18. View

Ferguson B, Mansur D, Peters N, Ren H, Smith G . DNA-PK is a DNA sensor for IRF-3-dependent innate immunity. Elife. 2012; 1:e00047. PMC: 3524801. DOI: 10.7554/eLife.00047. View

10.

Jeanson A, Tomasini P, Souquet-Bressand M, Brandone N, Boucekine M, Grangeon M . Efficacy of Immune Checkpoint Inhibitors in KRAS-Mutant Non-Small Cell Lung Cancer (NSCLC). J Thorac Oncol. 2019; 14(6):1095-1101. DOI: 10.1016/j.jtho.2019.01.011. View

11.

Barber G . STING-dependent cytosolic DNA sensing pathways. Trends Immunol. 2013; 35(2):88-93. DOI: 10.1016/j.it.2013.10.010. View

12.

Nascimento M, Gombault A, Lacerda-Queiroz N, Panek C, Savigny F, Sbeity M . Self-DNA release and STING-dependent sensing drives inflammation to cigarette smoke in mice. Sci Rep. 2019; 9(1):14848. PMC: 6795997. DOI: 10.1038/s41598-019-51427-y. View

13.

Tabibzadeh S . Homeostasis of extracellular matrix by TGF-beta and lefty. Front Biosci. 2002; 7:d1231-46. DOI: 10.2741/a836. View

14.

Huang X, Yang Y . Targeting the TLR9-MyD88 pathway in the regulation of adaptive immune responses. Expert Opin Ther Targets. 2010; 14(8):787-96. PMC: 2917181. DOI: 10.1517/14728222.2010.501333. View

15.

Zhu H, Zhao M, Chang C, Chan V, Lu Q, Wu H . The complex role of AIM2 in autoimmune diseases and cancers. Immun Inflamm Dis. 2021; 9(3):649-665. PMC: 8342223. DOI: 10.1002/iid3.443. View

16.

Ye L, Schnepf D, Staeheli P . Interferon-λ orchestrates innate and adaptive mucosal immune responses. Nat Rev Immunol. 2019; 19(10):614-625. DOI: 10.1038/s41577-019-0182-z. View

17.

Ferreira-Coimbra J, Sarda C, Rello J . Burden of Community-Acquired Pneumonia and Unmet Clinical Needs. Adv Ther. 2020; 37(4):1302-1318. PMC: 7140754. DOI: 10.1007/s12325-020-01248-7. View

18.

Skoulidis F, Goldberg M, Greenawalt D, Hellmann M, Awad M, Gainor J . Mutations and PD-1 Inhibitor Resistance in -Mutant Lung Adenocarcinoma. Cancer Discov. 2018; 8(7):822-835. PMC: 6030433. DOI: 10.1158/2159-8290.CD-18-0099. View

19.

Motwani M, Pawaria S, Bernier J, Moses S, Henry K, Fang T . Hierarchy of clinical manifestations in SAVI N153S and V154M mouse models. Proc Natl Acad Sci U S A. 2019; 116(16):7941-7950. PMC: 6475399. DOI: 10.1073/pnas.1818281116. View

20.

Marcus A, Mao A, Lensink-Vasan M, Wang L, Vance R, Raulet D . Tumor-Derived cGAMP Triggers a STING-Mediated Interferon Response in Non-tumor Cells to Activate the NK Cell Response. Immunity. 2018; 49(4):754-763.e4. PMC: 6488306. DOI: 10.1016/j.immuni.2018.09.016. View