Leveraging Genetics to Investigate Causal Effects of Immune Cell Phenotypes in Periodontitis: a Mendelian Randomization Study

Overview

Journal Front Genet

Date 2024 Jul 8

PMID 38974387

Authors

Yingjie Bai

Pengxian Xie

Ziyu Jin

Shengao Qin

Guowu Ma

Affiliations

Soon will be listed here.

Abstract

Introduction: Immune cells are dynamic in the inflammatory environment and play a key role in eradicating periodontal pathogens, modulating immune responses, and instigating tissue destruction. Identifying specific immune cell phenotypes associated with periodontitis risk is essential for targeted immunotherapeutic interventions. However, the role of certain specific immune cell phenotypes in the development of periodontitis is unknown. Mendelian randomization offers a novel approach to reveal causality and address potential confounding factors through genetic instruments.

Methods: This two-sample Mendelian randomization study assessed the causal relationship between 731 immune cell phenotypes and periodontitis using the inverse variance weighting method with the GWAS catalog genetic database. Methodological robustness was ensured through Cochran's Q test, MR-Egger regression, MR-PRESSO, and Leave-One-Out analysis.

Results: 14 immune cell phenotypes showed potential positive causal associations with periodontitis risk ( < 0.05), suggesting an increased risk, while 11 immune cell phenotypes exhibited potential negative causal associations ( < 0.05), indicating a reduced risk. No significant heterogeneity or pleiotropy was observed.

Conclusion: This study underscores certain immune cell types as potential periodontitis risk biomarkers, laying a theoretical foundation for future individualized treatment and precision medicine development.

References

Chen H, Peng L, Wang Z, He Y, Tang S, Zhang X . Exploration of cross-talk and pyroptosis-related gene signatures and molecular mechanisms between periodontitis and diabetes mellitus via peripheral blood mononuclear cell microarray data analysis. Cytokine. 2022; 159:156014. DOI: 10.1016/j.cyto.2022.156014. View

Cavalla F, Hernandez M . Polarization Profiles of T Lymphocytes and Macrophages Responses in Periodontitis. Adv Exp Med Biol. 2022; 1373:195-208. DOI: 10.1007/978-3-030-96881-6_10. View

Hogquist K, Xing Y, Hsu F, Shapiro V . T Cell Adolescence: Maturation Events Beyond Positive Selection. J Immunol. 2015; 195(4):1351-7. PMC: 4530466. DOI: 10.4049/jimmunol.1501050. View

Jagannathan R, Lavu V, Ranga Rao S . Comparison of the proportion of non-classic (CD14+CD16+) monocytes/macrophages in peripheral blood and gingiva of healthy individuals and patients with chronic periodontitis. J Periodontol. 2013; 85(6):852-8. DOI: 10.1902/jop.2013.120658. View

Yuan S, Wei Y, Jiang W, Sun F, Li S, Li Q . CCR2 is a potential therapeutic target in peri-implantitis. J Clin Periodontol. 2023; 51(3):354-364. DOI: 10.1111/jcpe.13916. View

Mionnet C, Buatois V, Kanda A, Milcent V, Fleury S, Lair D . CX3CR1 is required for airway inflammation by promoting T helper cell survival and maintenance in inflamed lung. Nat Med. 2010; 16(11):1305-12. DOI: 10.1038/nm.2253. View

El-Awady A, Elashiry M, Morandini A, Meghil M, Cutler C . Dendritic cells a critical link to alveolar bone loss and systemic disease risk in periodontitis: Immunotherapeutic implications. Periodontol 2000. 2022; 89(1):41-50. PMC: 9018591. DOI: 10.1111/prd.12428. View

Sima C, Viniegra A, Glogauer M . Macrophage immunomodulation in chronic osteolytic diseases-the case of periodontitis. J Leukoc Biol. 2018; 105(3):473-487. PMC: 6386606. DOI: 10.1002/JLB.1RU0818-310R. View

Kawai T, Matsuyama T, Hosokawa Y, Makihira S, Seki M, Karimbux N . B and T lymphocytes are the primary sources of RANKL in the bone resorptive lesion of periodontal disease. Am J Pathol. 2006; 169(3):987-98. PMC: 1698808. DOI: 10.2353/ajpath.2006.060180. View

10.

Burgess S, Butterworth A, Thompson S . Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol. 2013; 37(7):658-65. PMC: 4377079. DOI: 10.1002/gepi.21758. View

11.

Bowden J, Davey Smith G, Haycock P, Burgess S . Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator. Genet Epidemiol. 2016; 40(4):304-14. PMC: 4849733. DOI: 10.1002/gepi.21965. View

12.

Gunderson A, Mohammed J, Horvath F, Podolsky M, Anderson C, Glick A . CD8(+) T cells mediate RAS-induced psoriasis-like skin inflammation through IFN-γ. J Invest Dermatol. 2012; 133(4):955-63. PMC: 3577939. DOI: 10.1038/jid.2012.390. View

13.

Jiang W, Xu T, Yuan S, Wei Y, Song Z, Li Q . Critical roles for CCR2 and the therapeutic potential of cenicriviroc in periodontitis: A pre-clinical study. J Clin Periodontol. 2022; 49(11):1203-1216. DOI: 10.1111/jcpe.13699. View

14.

Piedra-Quintero Z, Wilson Z, Nava P, Guerau-de-Arellano M . CD38: An Immunomodulatory Molecule in Inflammation and Autoimmunity. Front Immunol. 2020; 11:597959. PMC: 7734206. DOI: 10.3389/fimmu.2020.597959. View

15.

Davies N, Holmes M, Davey Smith G . Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ. 2018; 362:k601. PMC: 6041728. DOI: 10.1136/bmj.k601. View

16.

Fang P, Li X, Dai J, Cole L, Camacho J, Zhang Y . Immune cell subset differentiation and tissue inflammation. J Hematol Oncol. 2018; 11(1):97. PMC: 6069866. DOI: 10.1186/s13045-018-0637-x. View

17.

Gonzales J . T- and B-cell subsets in periodontitis. Periodontol 2000. 2015; 69(1):181-200. DOI: 10.1111/prd.12090. View

18.

Morimura S, Oka T, Sugaya M, Sato S . CX3CR1 deficiency attenuates imiquimod-induced psoriasis-like skin inflammation with decreased M1 macrophages. J Dermatol Sci. 2016; 82(3):175-88. DOI: 10.1016/j.jdermsci.2016.03.004. View

19.

Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M . CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med. 2009; 15(8):914-20. DOI: 10.1038/nm.1964. View

20.

Loos B, Van Dyke T . The role of inflammation and genetics in periodontal disease. Periodontol 2000. 2020; 83(1):26-39. PMC: 7319430. DOI: 10.1111/prd.12297. View