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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:Sexual dimorphism in skin immunity is mediated by androgen-ILC2-dendritic cell axis
| PRJNA1064986 | ENA
Project description:Sexual dimorphism in skin immunity is mediated by androgen-ILC2-dendritic cell axis [scRNA-seq]
| PRJNA1064988 | ENA
Project description:Sexual dimorphism in skin immunity is mediated by androgen-ILC2-dendritic cell axis [Bulk RNA-seq]
| PRJNA1064989 | ENA
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:Sexual dimorphisms can be seen in many organisms with some exhibiting subtle differences while some can be very evident. The difference between male and female can be seen on the morphological level such as discrepancies in body mass, presence of body hair in distinct places, or through the presence of specific reproductive structures. It is known that the development of the reproductive structures is governed by hormone signaling, most commonly explained through the actions of androgen signaling. The developmental program of the male and female external genitalia involves a common anlage, the genital tubercle or GT, that later on develop into a penis and clitoris, respectively. Androgen signaling involvement can be seen in the different tissues in the GT that express Androgen receptor and the different genes that are regulated by androgen in the mesenchyme and endoderm component of the GT. Muscles are also known to be responsive to androgen signaling with male and female muscles exhibiting different capabilities. However, the occurrence of sexual dimorphism in muscle development is unclear. In this minireview, a summary on the role of androgen in the sexually dimorphic development of the genital tubercle was provided. This was used as a framework on analyzing the different mechanism employed by androgen signaling to regulate the sexual dimorphism in muscle development.
| S-EPMC9379613 | 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:Males are generally more susceptible to impaired glucose metabolism and type 2 diabetes (T2D) than females. However, the underlying mechanisms remain to be determined. Here, we revealed that gut microbiome depletion abolished sexual dimorphism in glucose metabolism. The transfer of male donor microbiota into antibiotics-treated female mice led the recipients to be more insulin resistant. Depleting androgen via castration changed the gut microbiome of male mice to be more similar to that of females and improved glucose metabolism, while reintroducing dihydrotestosterone (DHT) reversed these alterations. More importantly, the effects of androgen on glucose metabolism were largely abolished when the gut microbiome was depleted. Next, we demonstrated that androgen modulated circulating glutamine and glutamine/glutamate (Gln/Glu) ratio partially depending on the gut microbiome, and glutamine supplementation increases insulin sensitivity in vitro. Our study identifies the effects of androgen in deteriorating glucose homeostasis partially by modulating the gut microbiome and circulating glutamine and Gln/Glu ratio, thereby contributing to the difference in glucose metabolism between the two sexes.
| S-EPMC8648805 | 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