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Project description:Males and females exhibit profound differences in immune responses and disease susceptibility. However, the factors responsible for sex differences in tissue immunity remain poorly understood. Here, we uncover a dominant role for type 2 innate lymphoid cells (ILC2) in shaping sexual immune dimorphism within the skin. Mechanistically, negative regulation of ILC2 by androgens leads to a reduction in dendritic cell (DC) accumulation and activation in males, and reduced tissue immunity. Collectively, this work uncovers an androgen-ILC2-DC axis in controlling sexual immune dimorphism. Moreover, this work proposes that tissue immune set-points are defined by the dual action of sex hormones and the microbiota, with sex hormones controlling the strength of local immunity and microbiota calibrating its tone.
2024-04-09 | GSE253294 | GEO
Project description:Males and females exhibit profound differences in immune responses and disease susceptibility. However, the factors responsible for sex differences in tissue immunity remain poorly understood. Here, we uncover a dominant role for type 2 innate lymphoid cells (ILC2) in shaping sexual immune dimorphism within the skin. Mechanistically, negative regulation of ILC2 by androgens leads to a reduction in dendritic cell (DC) accumulation and activation in males, and reduced tissue immunity. Collectively, this work uncovers an androgen-ILC2-DC axis in controlling sexual immune dimorphism. Moreover, this work proposes that tissue immune set-points are defined by the dual action of sex hormones and the microbiota, with sex hormones controlling the strength of local immunity and microbiota calibrating its tone.
2024-04-09 | GSE253293 | GEO
Project description:BackgroundSexual dimorphism in immunity is believed to reflect sex differences in reproductive strategies and trade-offs between competing life history demands. Sexual selection can have major effects on mating rates and sex-specific costs of mating and may thereby influence sex differences in immunity as well as associated host-pathogen dynamics. Yet, experimental evidence linking the mating system to evolved sexual dimorphism in immunity are scarce and the direct effects of mating rate on immunity are not well established. Here, we use transcriptomic analyses, experimental evolution and phylogenetic comparative methods to study the association between the mating system and sexual dimorphism in immunity in seed beetles, where mating causes internal injuries in females.ResultsWe demonstrate that female phenoloxidase (PO) activity, involved in wound healing and defence against parasitic infections, is elevated relative to males. This difference is accompanied by concomitant sex differences in the expression of genes in the prophenoloxidase activating cascade. We document substantial phenotypic plasticity in female PO activity in response to mating and show that experimental evolution under enforced monogamy (resulting in low remating rates and reduced sexual conflict relative to natural polygamy) rapidly decreases female (but not male) PO activity. Moreover, monogamous females had evolved increased tolerance to bacterial infection unrelated to mating, implying that female responses to costly mating may trade off with other aspects of immune defence, an hypothesis which broadly accords with the documented sex differences in gene expression. Finally, female (but not male) PO activity shows correlated evolution with the perceived harmfulness of male genitalia across 12 species of seed beetles, suggesting that sexual conflict has a significant influence on sexual dimorphisms in immunity in this group of insects.ConclusionsOur study provides insights into the links between sexual conflict and sexual dimorphism in immunity and suggests that selection pressures moulded by mating interactions can lead to a sex-specific mosaic of immune responses with important implications for host-pathogen dynamics in sexually reproducing organisms.
| S-EPMC8170964 | biostudies-literature
Project description:Sex differences are well known to be determinants of development, health and disease. Epigenetic mechanisms are also known to differ between men and women through X-inactivation in females. We hypothesized that epigenetic sex differences may also result from sex hormone functions, in particular from long-lasting androgen programming. We aimed at investigating whether inactivation of the androgen receptor, the key regulator of normal male sex development, is associated with differences of the patterns of DNA methylation marks in genital tissues. To this end, we performed large scale array-based analysis of gene methylation profiles on genomic DNA from labioscrotal skin fibroblasts of 8 males and 26 individuals with androgen insensitivity syndrome (AIS) due to inactivating androgen receptor gene mutations. By this approach we identified differential methylation of 167 CpG loci representing 162 unique human genes. These were significantly enriched for androgen target genes and low CpG content promoter genes. Additional 75 genes showed a significant increase of heterogeneity of methylation in AIS compared to a high homogeneity in normal male controls. Our data show that normal and aberrant androgen receptor function is associated with distinct patterns of DNA-methylation marks in genital tissues. These findings support the concept that transcription factor binding to the DNA has an impact on the shape of the DNA methylome. These data which derived from a rare human model suggest that androgen programming of methylation marks contributes to sexual dimorphism in the human which might have considerable impact on the manifestation of sex-associated phenotypes and diseases.
| S-EPMC3762730 | biostudies-literature
Project description:To decipher hormonal from chromosomal factors we compared DNA-methylation of 27,568 CpG-loci in genital fibroblasts from 46,XY feminized individuals (AIS) with inactivating androgen receptor mutations to those of normal males. The results of the following two subset comparisons are linked to the Series record below: CpG loci differentially methylated (q<0.04) between AIS and male controls (primary human genital fibroblasts): To decipher hormonal from chromosomal factors we compared DNA-methylation of 27,568 CpG-loci in genital fibroblasts from 46,XY feminized individuals (AIS) with inactivating androgen receptor mutations to those of normal males. Cell culture of primary fibroblasts from scrotum/ labia majora from donors with PAIS (n=13), MAIS (n=1) or CAIS (n=13) and 9 controls were analyzed using the HumanMethylation27 Bead Chip. 13 AIS samples and all controls were analyzed in duplicates. Samples with gene call rates <95% as analyzed with BeadStudio software (Illumina, Inc.) and CpGs with detection p-values >0.05 in at least one experiment were excluded from analyses. 54 hybridizations with 25,988 CpGs entered the analysis. Differential methylation analysis (DMA) was performed based on average beta-values were performed using OMICS Explorer (v.2.1(25); Qlucore, Sweden). This file contains CpG loci found differentially methylated (q<0.04) by this approach. CpG loci characterized by a high varibility in their DNA methylation value in AIS compared to male controls (primary human genital fibroblasts): To decipher hormonal from chromosomal factors we compared DNA-methylation of 27,568 CpG-loci in genital fibroblasts from 46,XY feminized individuals (AIS) with inactivating androgen receptor mutations to those of normal males. Cell culture of primary fibroblasts from scrotum/ labia majora from donors with PAIS (n=13), MAIS (n=1) or CAIS (n=13) and 9 controls were analyzed using the HumanMethylation27 Bead Chip. 13 AIS samples and all controls were analyzed in duplicates. Samples with gene call rates <95% as analyzed with BeadStudio software (Illumina, Inc.) and CpGs with detection p-values >0.05 in at least one experiment were excluded from analyses. 54 hybridizations with 25,988 CpGs entered the analysis. CpG loci with beta-values ranged in control samples up to 0.34 and a difference of the interquartiles between controls and AIS samples above 0.16 were considered as being variably methylated in AIS and are included in this file.
2012-08-12 | GSE31362 | GEO
Project description:To investigate sexual dimorphism and postnatal changes in skin collagen expression, mRNA levels of collagens and their regulatory factors in male and female skin were examined during the first 120 days of age by quantitative realtime PCR. Levels of mRNAs encoding extracellular matrices did not show any differences between male and female mice until day 15. Col1a1 and Col1a2 mRNAs noticeably increased at day 30 and remained at high levels until day 120 in male mice, while those in female mice remained at low levels during the period. Consistent with the mRNA expression, pepsin-soluble type I collagen contents in skin was very high in mature male as compared to female. Col3a1 mRNA in male mice also showed significantly high level at day 120 as compared to female. On the other hand, expression of mRNAs encoding TGF-ßs and their receptors did not show apparent sexual dimorphism although small significant differences were observed at some points. Castration at 60 days of age resulted in a significant decrease in type I collagen mRNA expression within 3 days, and noticeably decreased expression of all fibril collagen mRNAs examined within 14 days, while administration of testosterone tube maintained the mRNA expression at high levels. Despite the in vivo effect of testosterone, administration of physiological concentrations of testosterone did not affect fibril collagen mRNA expression in either human or mouse skin fibroblasts in vitro, suggesting that testosterone does not directly affect collagen expression in fibroblasts. In summary, present study demonstrated dynamic postnatal changes in expression of collagens and their regulatory factors, and suggest that testosterone and its effects on collagen expression are responsible for the skin sexual dimorphism but the effects of testosterone is not due to direct action on dermal fibroblasts.
| S-EPMC5426772 | biostudies-literature
Project description:Weakly-electric fish (Apteronotidae) produce highly diverse electrocommunication signals. Electric organ discharges (EODs) vary across species, sexes, and in the magnitude and direction of their sexual dimorphism. Gonadal steroid hormones can modulate EODs, and differences in androgen sensitivity are hypothesized to underlie variation in the degree of sexual dimorphism across species. In this study, we asked whether variation in androgen sensitivity explained variation in sexual dimorphism of EODs within species, at the population level. We examined two populations of black ghost knifefish (Apteronotus albifrons), one from the Orinoco and the other from the Amazon River Basin. EOD frequency (EODf) and chirp rates were measured to characterize diversity in sexual dimorphism across populations. The magnitude of sexual dimorphism in EODf differed significantly across populations, and was more pronounced in the Orinoco population than in the Amazon population. Chirp rates were sexually monomorphic in both populations. 11-Ketotestosterone (11-kT) was administered over a two-week period to assess population differences in sensitivity to androgens. 11-kT masculinized EODf significantly more in the population with the greater degree of sexual dimorphism. 11-kT had no effect on the sexually monomorphic chirping rates. We conclude that population divergence in androgen sensitivity contributes to variation in sexual dimorphism of EODf in A. albifrons.
| S-EPMC3570824 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-04-13 | GSE222792 | GEO
Project description:Autoimmune diseases affect 5% to 8% of the population, and females are more susceptible to these diseases than males. Here, we analyzed human thymic transcriptome and revealed sex-associated differences in the expression of tissue-specific antigens that are controlled by the autoimmune regulator (AIRE), a key factor in central tolerance. We hypothesized that the level of AIRE is linked to sexual dimorphism susceptibility to autoimmune diseases. In human and mouse thymus, females expressed less AIRE (mRNA and protein) than males after puberty. These results were confirmed in purified murine thymic epithelial cells (TECs). We also demonstrated that AIRE expression is related to sexual hormones, as male castration decreased AIRE thymic expression and estrogen receptor ?-deficient mice did not show a sex disparity for AIRE expression. Moreover, estrogen treatment resulted in downregulation of AIRE expression in cultured human TECs, human thymic tissue grafted to immunodeficient mice, and murine fetal thymus organ cultures. AIRE levels in human thymus grafted in immunodeficient mice depended upon the sex of the recipient. Estrogen also upregulated the number of methylated CpG sites in the AIRE promoter. Together, our results indicate that in females, estrogen induces epigenetic changes in the AIRE gene, leading to reduced AIRE expression under a threshold that increases female susceptibility to autoimmune diseases.
| S-EPMC4811157 | biostudies-literature
Project description:The skin contains readily accessible dendritic cells (DCs) with potent antigen presentation function and functional plasticity enabling the integration of antigen specificity with environmentally responsive immune control. Recent studies challenge the established paradigm of cutaneous immune function by suggesting that lymph node-resident DCs, rather than skin-derived DCs (sDCs), are responsible for eliciting T cell immunity against cutaneous pathogens including viral vectors. We show that cutaneous delivery of lentivirus results in direct transfection of sDCs and potent and prolonged antigen presentation. Further, sDCs are the predominant antigen-presenting cells for the induction of potent and durable CD8(+) T cell immunity. These results support the classical paradigm of cutaneous immune function and suggest that antigen presentation by sDCs contributes to the high potency of lentivector-mediated genetic immunization.
| S-EPMC3077717 | biostudies-literature