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RNA-sequencing of bulk CD19+ Thymic B cells from young (5 week) and aged (10-24 month) mice

ABSTRACT: Thymic B cells have been recently shown the ability to be licensed to express Aire, a critical transcription factor involved in the expression of self-antigens in the thymus which are critical for clonal deletion of autoreactive T cells and maintenance of self-tolerance. Mutations in AIRE cause systemic autoimmunity in humans and autoimmunity with varying degrees of severity in different mouse strains. Thymic B cells have been studied in young animals, but studies of this population with age are lacking. Given the thymus undergoes age-associated atrophy in its stromal compartment, we hypothesized that aged thymic B cells may under go changes with age which may impact their ability to mediate clonal deletion of autoreactive T cells and may contribute to age-associated increases in autoimmune prevalence. By comparing the transcriptome of young and aged thymic B cells we find that Aire and transcriptional activators of Aire are signficantly decreased with age.

ORGANISM(S): Mus musculus

PROVIDER: GSE107110 | GEO | 2018/01/30

REPOSITORIES: GEO

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RNA-sequencing of bulk CD19+ Thymic B cells from young (3 month - 4 year) and old (42 - 61 years) humans

Project description:Thymic B cells have been recently shown the ability to be licensed to express Aire, a critical transcription factor involved in the expression of self-antigens in the thymus which are critical for clonal deletion of autoreactive T cells and maintenance of self-tolerance. Mutations in AIRE cause systemic autoimmunity in humans and autoimmunity with varying degrees of severity in different mouse strains. Thymic B cells have been studied in young animals, but studies of this population with age are lacking. Given the thymus undergoes age-associated atrophy in its stromal compartment, we hypothesized that aged thymic B cells may under go changes with age which may impact their ability to mediate clonal deletion of autoreactive T cells and may contribute to age-associated increases in autoimmune prevalence. By comparing the transcriptome of young and aged thymic B cells we find that Aire and transcriptional activators of Aire are signficantly decreased with age.

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Project description:AIRE expression in thymus is downregulated by estrogen after puberty, what probably renders women more susceptible to autoimmune disorders. Here we investigated the effects of minipuberty on male and female infant human thymic tissue in order to verify if this initial transient increase in sex hormones - along the first six months of life - could affect thymic transcriptional network regulation and AIRE expression. Gene co-expression network analysis for differentially expressed genes and miRNA-target analysis revealed sex differences in thymic tissue during minipuberty, but such sex differences were not detected in thymic tissues from donors aged 7-18 moths of age, the non-puberty group. AIRE expression was essentially the same in both sexes in minipuberty and in non-puberty groups, as assessed by genomic and immunohistochemical assays. However, AIRE-interactors networks showed several differences in all groups regarding gene-gene expression correlation. Therefore, minipuberty and genomic mechanisms interact in shaping thymic sexual dimorphism along the first six moths of life.

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