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.

项目总结 变性人是出生时就被分配了性别，但由于他们的 经历的性别与他们分配的性别不一致。治疗性别焦虑症的一种方法是 使用性别肯定荷尔蒙疗法来促进理想性行为的身体特征。这是高度 与艾滋病毒疫苗反应中出现的二元(例如男性/女性)性别特定差异有关， 暴露前的预防效果、病毒致病机制和病毒库，这可能至少部分地归因于， 性激素。事实上，性激素驱动的免疫细胞内转录和功能的多样性 变性人的直肠粘膜(RM)可能对HIV的预防和治疗产生深远的影响 针对这些人群的战略。这是一个强有力的论据，证明了基础、基础研究的迫切需要 进入单细胞转录和居住在RM的免疫细胞的功能分析，跨越性别和性别 频谱。在目标1中，我们将重点定义适应性免疫细胞的性别和性别特征 来自顺性别男性和女性以及跨性别男性和女性，通过高分辨率的单细胞 转录学。在目标2中，我们将定义先天免疫的性别和性别特异性转录特征。 细胞，以及量化性别和性别差异的NK细胞功能。更全面地了解 性激素谱和性染色体对免疫系统的影响将促进战略性艾滋病毒 适合跨性别者的预防和治疗战略。