Age-Related Changes on CD40 Promotor Methylation and Immune Gene Expressions in Thymus of Chicken

Abstract

One hundred and twenty one-day-old breeder cocks, included 15 cages of 8 birds each, were fed to learn the aging's effect on chicken's thymus immunity. At 2 (2-W) and 40 (40-W) weeks of age, one chicken each cage was randomly chosen and slaughtered to get the thymus sample. The results showed that thymus weight and morphology of 40-W group were far different from that of 2-W group, and exhibited a property of degeneration. Considering this phenotype variance, we analyzed the thymus' transcriptome to investigate the molecular mechanism that had been implicated in this phenotype diversity with age. Pearson correlation coefficients and principal component analysis indicated that two major populations corresponding to 40-W and 2-W group were identified, and 1949 differentially expressed genes (DEGs, 1722 up-regulated and 127 down-regulated) were obtained. Results of GO and KEGG pathway enrichment found that 4 significantly enriched KEGG pathways (Cytokine-cytokine receptor interaction, Intestinal immune network for IgA production, Toll-like receptor signaling pathway, AGE-RAGE signaling pathway in diabetic complications) related to immunoregulation were screened between 40-W and 2-W group. These results confirmed that thymus immunity of chickens had a strong age-related correlation. DEGs related to these 4 enriched KEGG pathways were suppressed in the thymus of 2-W group, this indicated that thymus immunity of 2-weeks-age chick was down-regulated. CD40 is involved in 3 of the 4 significantly enriched pathways, and it is critical for thymus immune-regulation. CD40 promoter methylation level of 2-W group was higher than that of 40-W group, it is consistent with the transcriptional differences of the gene. Our study concluded that thymus immunity of chicken was varied with age. Compared to the 40-W group, thymus immunity of 2-W group was down-regulated, and in a status of hypo-activation on the whole, and these effects might be related to CD40 suppression induced by promoter hyper-methylation of the gene.

Genome-Wide DNA Methylation Profile Indicates Potential Epigenetic Regulation of Aging in the Rhesus Macaque Thymus

“…Meanwhile, DEGs and hub DEGs identified based on transcriptome analysis were mostly enriched in immune (mainly complement system), clotting and other pathways. Our results implied that the thymus in adult macaques significantly changed in immune responsiveness, coagulation and hormonal endocrine activity compared with young macaques, which was consistent with results from previous physiological studies [ 33 , 34 , 35 ]. Combining data from DNA methylation and transcriptomes, we identified 431 overlapping genes of DMGs and DEGs, where 45 genes were related to immune functions.…”

“…Previous studies on the thymus of humans, chickens and mice indicated that the significant physiological changes in the thymus with age were the activation of the complement system, the enhancement of blood clotting and the changes in endocrine hormones [ 33 , 34 , 35 ]. We compared two young thymuses and two adult thymuses and identified 786 DEGs in the transcriptome analysis and 10,666 DMGs in the methylome analysis.…”

“…Samples were required to achieve an RNA integrity number (RIN) of at least 7.0, an OD260/280 value of 2.0 and an RNA concentration of at least 588 ng/μL using a NanoDrop2000 micro-spectrophotometer, Agilent RNA 6000 Nano Kit and Agilent 2100 Bioanalyzer (Agilent, Waldbroon, Germany) ( Supplementary Table S16 ). RNA library construction and sequencing were performed using the same protocols employed by a previous study [ 33 ]. All reads of the RNA sequence were unpublished data of the key laboratory of bio-resources and eco-environment of the Ministry of Education, College of Life Sciences, Sichuan University, China.…”

Indigenous, Yellow-Feathered Chickens Body Measurements, Carcass Traits, and Meat Quality Depending on Marketable Age

“…Tok et al [ 8 ] found that the feather quality of birds was related to age. Yuan et al [ 9 ] and Li et al [ 10 ] observed that age can influence vaccine susceptibility and thymus immunity in chickens. Park et al [ 11 ] suggested that an optimized marketable age would benefit slaughter and chilling for the sales of broilers.…”

New Perspectives on Avian Models for Studies of Basic Aging Processes

“…Ultimately, the generation of organspecific transcriptomes will be possible at various points in a model organism's life history, as well as under specific experimental conditions, including anti-aging interventions As the field has grown, the human aging transcriptome has been shown to be a robust tool for estimating the biological age of an individual [152], as well as measuring age-related changes in tissue-specific transcriptomes of model organisms such as monkeys [153], mice [154], D. melanogaster [155,156], C. elegans [157,158], and yeast [159]. Not surprisingly, relatively little is known about the aging transcriptome in birds, with the exception of studies of brain [160] and thymus [161] transcriptomes in populations of domestic chicken. Dramatic differences in the basic genomics of wild vs. domesticated species may be problematic when trying to extrapolate findings from these studies to birds in general [162].…”