Gender as a biological variable: transcriptomic analysis of rectal mucosal immune cells among transgender people

性别作为生物变量：变性人直肠粘膜免疫细胞的转录组分析

• 批准号: 10376886
• 负责人: Colleen F Kelley
• 金额: $ 19.56万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10376886
• 关键词: AIDS prevention; Androgen Antagonists; B-Lymphocytes; Biological; Biological Assay; Biomedical Research; Birth; Blood; CD22 gene; CD28 gene; CD80 gene; CTLA4 gene; CXCR3 gene; Cell physiology; Cells; Characteristics; Chromosomes; Data; ESR1 gene; ESR2 gene; Ensure; Environment; Estrogen Receptors; Estrogens; Female; Foundations; Funding; Gender; Gender Identity; Gene Expression; Genes; Goals; Gonadal Steroid Hormones; HIV; HIV Infections; HIV vaccine; IL2RG gene; Immune; Immune system; Immunologics; Immunology; Individual; Innate Immune System; Intervention; Investigation; Light; Mediating; MicroRNAs; Modeling; Mucous Membrane; Natural Killer Cells; Outcome; Parents; Pathogenesis; Pathway interactions; Persons; Population; Prevention strategy; Public Health; Research; Resolution; Sex Chromosomes; Sex Differences; Site; TLR7 gene; TNFSF5 gene; Testosterone; Tissues; United States National Institutes of Health; Untranslated RNA; Viral Pathogenesis; Viral reservoir; X Chromosome; cis-female; cis-male; cisgender; design; differential expression; dysphoria; experience; gender difference; gender dysphoria; hormone therapy; immunological diversity; immunoregulation; interest; male; memory CD4 T lymphocyte; microbiome; pre-exposure prophylaxis; programmed cell death protein 1; rectal; sex; single cell analysis; transcription factor; transcriptome; transcriptomics; transgender; transgender men; transgender women; transmission process; treatment strategy; vaccine response; xenoestrogen

Project summary Transgender persons are individuals who were assigned a sex at birth, but experience dysphoria due to their experienced gender not aligning with their assigned sex. One avenue of treatment for gender dysphoria is the use of gender affirming hormone therapy to promote the physical characteristics of the desired sex. This is highly relevant in light of the emerging binary (e.g. male/female) sex-specific differences in HIV vaccine responses, pre-exposure prophylaxis efficacy, viral pathogenesis, and viral reservoir, that may be attributed, at least in part, to sex hormones. Indeed, sex hormone-driven transcriptomic and functional diversity of immune cells within the rectal mucosa (RM) of transgender individuals could have a profound impact on HIV prevention and treatment strategies for theses populations. This is a strong argument for a critical need for basic, foundational research into single-cell transcriptomics and functional assays of RM-residing immune cells, across the gender and sex spectrum. In Aim 1, we will focus on defining the gender- and sex-specific features of adaptive immune cells from cisgender men and women, as well as transgender men and women, via high-resolution, single-cell transcriptomics. In Aim 2, we will define the gender- and sex-specific transcriptomic features of innate immune cells, as well as quantifying gender and sex differences in NK cell function. A more complete understanding of the spectrum of sex-hormone and sex-chromosome influence on the immune system will facilitate strategic HIV prevention and treatment strategies appropriate for transgender individuals.

项目摘要 跨性别者是在出生时被分配的个人，但由于他们的烦躁不安 经验丰富的性别不与分配的性别保持一致。性别烦躁不安的治疗途径是 使用性别确认激素疗法来促进所需性别的身体特征。这是高度的 鉴于新兴的二进制（例如男性/女性）性别特异性差异， 暴露前的预防疗效，病毒发病机理和病毒储存剂，至少部分归因于 到性激素。实际上，性激素驱动的转录组和功能多样性 跨性别者的直肠粘膜（RM）可能对预防HIV和治疗产生深远的影响 这些人群的策略。这是对基础，基础研究的批判性需求的强烈论点 分解单细胞转录组学和跨性别和性别的RM免疫细胞的功能测定 光谱。在AIM 1中，我们将专注于定义适应性免疫细胞的性别和性别特异性特征 来自Cisgender的男女，以及跨性别的男人和女人，通过高分辨率，单细胞 转录组学。在AIM 2中，我们将定义先天免疫的性别和性别特定的转录组特征 细胞，以及量化NK细胞功能的性别和性别差异。对 性激素和性染色体对免疫系统的影响将有助于战略艾滋病毒 适合跨性别者的预防和治疗策略。