Cytokines mapping for tissue-specific expression, eQTLs and GWAS traits

Abstract

Dysregulation in cytokine production has been linked to the pathogenesis of various immune-mediated traits, in which genetic variability contributes to the etiopathogenesis. GWA studies have identified many genetic variants in or near cytokine genes, nonetheless, the translation of these findings into knowledge of functional determinants of complex traits remains a fundamental challenge. In this study we aimed at collection, analysis and interpretation of data on cytokines focused on their tissue-specific expression, eQTLs and GWAS traits. Using GO annotations, we generated a list of 314 cytokines and analyzed them with the GTEx resource. Cytokines were highly tissue-specific, 82.3% of cytokines had Tau expression metrics ≥ 0.8. In total, 3077 associations for 1760 unique SNPs in or near 244 cytokines were mapped in the NHGRI-EBI GWAS Catalog. According to the Experimental Factor Ontology resource, the largest numbers of disease associations were related to ‘Inflammatory disease’, ‘Immune system disease’ and ‘Asthma’. The GTEx-based analysis revealed that among GWAS SNPs, 1142 SNPs had eQTL effects and influenced expression levels of 999 eGenes, among them 178 cytokines. Several types of enrichment analysis showed that it was cytokines expression variability that fundamentally contributed to the molecular origins of considered immune-mediated conditions.

Early-life immune expression profiles predict later life health and fitness in a wild rodent

“…Here we provide a more refined analysis, and describe two examples in which differences detectable early in life in the expression of distinct immune pathways play out much later in life, or at least over a much more extended period. Il10 differences confirm a genetic basis for immune expression that, as previously shown in this system and others, act through the network of interacting cytokines such that polymorphism at one cytokine gene can affect expression of other cytokines and immune phenotypes 23,[51][52][53][54][55][56] , with these effects further percolating to affect health and fitness more broadly in later life. By contrast, the Il17 differences appear to be more reminiscent of the Jesuit motto "Give me the boy until he is seven and I will give you the man": that independently of any genetic differences, an individual's experiences early in life may, in this case through the medium of immune expression, profoundly influence their later health and fitness.…”

Early‐life immune expression profiles predict later‐life health and fitness in a wild rodent

“…The observed genetic effect, as previously shown in the present system and others, acts through the network of interacting cytokines such that polymorphism at one cytokine gene can affect expression of other cytokines and immune phenotypes (Dinarello, 2007;Li et al, 2016;Salnikova et al, 2020;ter Horst et al, 2016;Turner et al, 2011;Viney & Riley, 2017;Wanelik et al, 2018).…”

NK cell education: Physiological and pathological influences

“…The differences in educated NK cell repertoires among diverse tissues could be due to variations in environmental factors (51). The environment can be heavily influenced by soluble factors that cause changes within immune cells (52,53).…”