Innate and Adaptive Immune Traits Are Differentially Affected by Genetic and Environmental Factors

Overview

Journal Nat Commun

Specialty Biology

Date 2017 Jan 6

PMID 28054551

Citations 71

Authors

Massimo Mangino

Mario Roederer

Margaret H Beddall

Frank O Nestle

Tim D Spector

Affiliations

Soon will be listed here.

Abstract

The diversity and activity of leukocytes is controlled by genetic and environmental influences to maintain balanced immune responses. However, the relative contribution of environmental compared with genetic factors that affect variations in immune traits is unknown. Here we analyse 23,394 immune phenotypes in 497 adult female twins. 76% of these traits show a predominantly heritable influence, whereas 24% are mostly influenced by environment. These data highlight the importance of shared childhood environmental influences such as diet, infections or microbes in shaping immune homeostasis for monocytes, B1 cells, γδ T cells and NKT cells, whereas dendritic cells, B2 cells, CD4 T and CD8 T cells are more influenced by genetics. Although leukocyte subsets are influenced by genetics and environment, adaptive immune traits are more affected by genetics, whereas innate immune traits are more affected by environment.

Citing Articles

Endophenotype 2.0: updated definitions and criteria for endophenotypes of psychiatric disorders, incorporating new technologies and findings.

Liu C, Gershon E Transl Psychiatry. 2024; 14(1):502.

PMID: 39719446 PMC: 11668880. DOI: 10.1038/s41398-024-03195-1.

Spatially resolved single-cell atlas unveils a distinct cellular signature of fatal lung COVID-19 in a Malawian population.

Nyirenda J, Hardy O, Da Silva Filho J, Herder V, Attipa C, Ndovi C Nat Med. 2024; 30(12):3765-3777.

PMID: 39567718 PMC: 11645280. DOI: 10.1038/s41591-024-03354-3.

Identifying genetic variants that influence the abundance of cell states in single-cell data.

Rumker L, Sakaue S, Reshef Y, Kang J, Yazar S, Alquicira-Hernandez J Nat Genet. 2024; 56(10):2068-2077.

PMID: 39327486 DOI: 10.1038/s41588-024-01909-1.

Maternal immune activation upregulates the AU020206-IRFs-STAT1 axis in modulating cytokine production in the brain.

Yang J, Yu W, Zhu R, Li S, Gao Y, Chen J Theranostics. 2024; 14(14):5682-5697.

PMID: 39310110 PMC: 11413792. DOI: 10.7150/thno.96110.

Integrated Germline and Somatic Features Reveal Divergent Immune Pathways Driving Response to Immune Checkpoint Blockade.

Sears T, Pagadala M, Castro A, Lee K, Kong J, Tanaka K Cancer Immunol Res. 2024; 12(12):1780-1795.

PMID: 39255339 PMC: 11612627. DOI: 10.1158/2326-6066.CIR-24-0164.

References

Andrew T, Hart D, Snieder H, de Lange M, Spector T, MacGregor A . Are twins and singletons comparable? A study of disease-related and lifestyle characteristics in adult women. Twin Res. 2002; 4(6):464-77. DOI: 10.1375/1369052012803. View

Carr E, Dooley J, Garcia-Perez J, Lagou V, Lee J, Wouters C . The cellular composition of the human immune system is shaped by age and cohabitation. Nat Immunol. 2016; 17(4):461-468. PMC: 4890679. DOI: 10.1038/ni.3371. View

Brodin P, Jojic V, Gao T, Bhattacharya S, Lopez Angel C, Furman D . Variation in the human immune system is largely driven by non-heritable influences. Cell. 2015; 160(1-2):37-47. PMC: 4302727. DOI: 10.1016/j.cell.2014.12.020. View

Moayyeri A, Hammond C, Valdes A, Spector T . Cohort Profile: TwinsUK and healthy ageing twin study. Int J Epidemiol. 2012; 42(1):76-85. PMC: 3600616. DOI: 10.1093/ije/dyr207. View

Marson A, Housley W, Hafler D . Genetic basis of autoimmunity. J Clin Invest. 2015; 125(6):2234-41. PMC: 4497748. DOI: 10.1172/JCI78086. View

Ahmadi K, Hall M, Norman P, Vaughan R, Snieder H, Spector T . Genetic determinism in the relationship between human CD4+ and CD8+ T lymphocyte populations?. Genes Immun. 2001; 2(7):381-7. DOI: 10.1038/sj.gene.6363796. View

Orru V, Steri M, Sole G, Sidore C, Virdis F, Dei M . Genetic variants regulating immune cell levels in health and disease. Cell. 2013; 155(1):242-56. PMC: 5541764. DOI: 10.1016/j.cell.2013.08.041. View

Neale M, Hunter M, Pritikin J, Zahery M, Brick T, Kirkpatrick R . OpenMx 2.0: Extended Structural Equation and Statistical Modeling. Psychometrika. 2015; 81(2):535-49. PMC: 4516707. DOI: 10.1007/s11336-014-9435-8. View

Docherty A, Kremen W, Panizzon M, Prom-Wormley E, Franz C, Lyons M . Comparison of Twin and Extended Pedigree Designs for Obtaining Heritability Estimates. Behav Genet. 2015; 45(4):461-6. PMC: 4459911. DOI: 10.1007/s10519-015-9720-z. View

10.

Kantor A, Herzenberg L . Layered evolution in the immune system. A model for the ontogeny and development of multiple lymphocyte lineages. Ann N Y Acad Sci. 1992; 651:1-9. DOI: 10.1111/j.1749-6632.1992.tb24588.x. View

11.

Fumagalli M, Sironi M, Pozzoli U, Ferrer-Admetlla A, Ferrer-Admettla A, Pattini L . Signatures of environmental genetic adaptation pinpoint pathogens as the main selective pressure through human evolution. PLoS Genet. 2011; 7(11):e1002355. PMC: 3207877. DOI: 10.1371/journal.pgen.1002355. View

12.

Roederer M, Quaye L, Mangino M, Beddall M, Mahnke Y, Chattopadhyay P . The genetic architecture of the human immune system: a bioresource for autoimmunity and disease pathogenesis. Cell. 2015; 161(2):387-403. PMC: 4393780. DOI: 10.1016/j.cell.2015.02.046. View

13.

Barreiro L, Quintana-Murci L . From evolutionary genetics to human immunology: how selection shapes host defence genes. Nat Rev Genet. 2009; 11(1):17-30. DOI: 10.1038/nrg2698. View

14.

Visscher P, Gordon S, Neale M . Power of the classical twin design revisited: II detection of common environmental variance. Twin Res Hum Genet. 2008; 11(1):48-54. PMC: 3996914. DOI: 10.1375/twin.11.1.48. View