Demographic and genetic factors influence the abundance of infiltrating immune cells in human tissues

Nat Commun. 2020 May 5;11(1):2213. doi: 10.1038/s41467-020-16097-9.

Abstract

Despite infiltrating immune cells having an essential function in human disease and patients' responses to treatments, mechanisms influencing variability in infiltration patterns remain unclear. Here, using bulk RNA-seq data from 46 tissues in the Genotype-Tissue Expression project, we apply cell-type deconvolution algorithms to evaluate the immune landscape across the healthy human body. We discover that 49 of 189 infiltration-related phenotypes are associated with either age or sex (FDR < 0.1). Genetic analyses further show that 31 infiltration-related phenotypes have genome-wide significant associations (iQTLs) (P < 5.0 × 10-8), with a significant enrichment of same-tissue expression quantitative trait loci in suggested iQTLs (P < 10-5). Furthermore, we find an association between helper T cell content in thyroid tissue and a COMMD3/DNAJC1 regulatory variant (P = 7.5 × 10-10), which is associated with thyroiditis in other cohorts. Together, our results identify key factors influencing inter-individual variability of immune infiltration, to provide insights on potential therapeutic targets.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Algorithms
  • Female
  • Gene Expression Profiling / methods*
  • Gene Regulatory Networks / genetics
  • Gene Regulatory Networks / immunology
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study / methods*
  • Genotype
  • Humans
  • Immune System / cytology
  • Immune System / immunology
  • Immune System / metabolism*
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Quantitative Trait Loci / genetics*
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / metabolism
  • Thyroid Gland / cytology
  • Thyroid Gland / immunology
  • Thyroid Gland / metabolism