Understanding the effects of cross-sex hormone therapy on vaginal mucosal immunity
了解跨性别激素治疗对阴道粘膜免疫的影响
基本信息
- 批准号:10749174
- 负责人:
- 金额:$ 26.7万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-08-14 至 2025-07-31
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAdultAffectAnal SexAreaBasic ScienceBiological AssayBiomedical ResearchBisexualBostonCellsChronicCommunitiesDNA Sequencing FacilityDataDevelopmentEstradiolFemaleFemale genitaliaGene ExpressionGene Expression ProfileGenitalGenitaliaGoalsGonadal Steroid HormonesHIVHIV InfectionsHIV riskHIV-1HealthHealthcareHeterosexualsHistologicHistologyHormonalHuman immunodeficiency virus testImmuneImmune responseImmune signalingImmunologicsImmunologyImpairmentIndividualInfectionKnowledgeLaboratoriesLactobacillusLigandsMasculineMedicalMeta-AnalysisMichiganModelingMucinsMucosal ImmunityMucous MembraneOrganismPenetrationPersonsPhysiologyPoly I-CPrevalenceRegimenReportingResearch PersonnelResearch PriorityResidual stateRiskRisk FactorsRoleSex OrientationSexual ReassignmentSexually Transmitted DiseasesSignal PathwaySterilitySurfaceTestingTestosteroneThickTissue ModelTissuesUnited StatesUnited States National Institutes of HealthUniversitiesVaginaWorkassigned female at birthchemokinecis-malecisgendercultural competencecytokinefemale sex hormonegender affirming hormone therapyhealth disparityhormone therapyinterestmale sex hormonesmarginalizationmicrobialnon-heterosexualpathogenreproductive tractresponsescreeningsexsexual risk behaviorsubstance usetranscriptomicstransgendertransgender mentransgender womentransmasculinetransmission processtumor-immune system interactionsvaginal microbiomevaginal mucosa
项目摘要
PROJECT SUMMARY/ABSTRACT
It is estimated that more than one million people in the United States identify as transgender. Despite recent
increased visibility, transgender individuals remain marginalized and subject to health disparities, and are
underrepresented in biomedical research. It is well documented that transgender persons are disproportionately
affected by HIV compared to their cisgender counterparts, but the basis for this is incompletely understood. In
particular, we have a very limited understanding of changes in mucosal immune defenses in the vaginal
compartment in transgender men and transmasculine individuals who receive chronic testosterone therapy as
part of gender affirming hormone therapy. This is relevant to understanding HIV risks as transgender men report
heterosexual, non-heterosexual, and bisexual orientation, making transgender men who have sex with cisgender
men a unique and understudied group. Our central hypothesis is that gender affirming hormone therapy in
transgender men leads to a dysregulated innate immune microenvironment and impaired barrier function of the
vaginal mucosal compartment, increasing the risk of HIV transmission during vaginal penetration. The goal of
this project is to characterize the effects of cross hormone therapy on the vaginal compartment using a
commercially available reconstructed vaginal tissue model that has been shown to be hormonally responsive
and support infection with HIV. We propose three aims to test our hypothesis. First, we will characterize the
histology of the testosterone dominant vagina in contrast to the estradiol primed vagina, looking at barrier
function, mucin expression, and steady state cytokine/chemokine release. The effects of testosterone on
colonization with lactobacillus will also be examined. Next, we will conduct transcriptomic studies to identify the
gene expression profile of the testosterone dominant vagina to identify changes in the immunologic signaling
pathways that could negatively impact host-pathogen interactions. Finally, we will examine HIV infection in the
testosterone dominant vagina in comparison to the estradiol primed vagina to determine if HIV transmission is
increased. At the completion of this project, we will have a broader understanding of the histologic and
immunologic effects of testosterone on the vaginal compartment, identifying defensive weaknesses in the
residual lower female genital tract in transgender men with an intact vagina that increase the risk of HIV
transmission. We believe our data will help inform the development of strategies for individuals undergoing
gender affirming hormone therapy to lessen the risk of HIV and other STI acquisition across this mucosal surface.
项目摘要/摘要
据估计,美国有超过一百万人被认定为变性人。尽管最近
尽管跨性别者的知名度提高,但他们仍然被边缘化,并受到健康差异的影响,
在生物医学研究中的代表性不足。有充分的证据表明,变性人不成比例地
与顺性别者相比,受艾滋病毒影响的妇女人数较少,但其基础尚不完全清楚。在
特别是,我们对阴道粘膜免疫防御的变化了解非常有限,
跨性别男性和接受长期睾酮治疗的跨男性个体中的隔室,
性别确认激素疗法的一部分这与理解跨性别男性报告的艾滋病毒风险有关
异性恋,非异性恋和双性恋取向,使变性人与顺性人发生性关系
男性是一个独特的未被充分研究的群体。我们的中心假设是,性别肯定激素治疗,
变性人导致先天免疫微环境失调,
阴道粘膜隔室,增加了在阴道插入过程中传播艾滋病毒的风险。的目标
该项目是使用一种新的方法来描述交叉激素治疗对阴道腔室的影响。
商业上可获得的重建的阴道组织模型,其已被证明是生殖反应性的
并支持艾滋病毒的感染。我们提出了三个目标来检验我们的假设。首先,我们将描述
睾酮主导阴道与雌二醇主导阴道的组织学对比,观察屏障
功能、粘蛋白表达和稳态细胞因子/趋化因子释放。睾丸激素对
此外,亦会研究细菌的定殖情况。下一步,我们将进行转录组学研究,以确定
睾酮主导阴道的基因表达谱,以确定免疫信号传导的变化
可能对宿主-病原体相互作用产生负面影响的途径。最后,我们将研究艾滋病毒感染的
睾酮主导的阴道与雌二醇主导的阴道进行比较,以确定HIV传播是否
增加该项目完成后,我们将对组织学和组织学有更广泛的了解。
睾丸激素对阴道隔室的免疫作用,确定阴道隔室的防御弱点,
具有完整阴道的变性男性的残留下女性生殖道增加了艾滋病毒的风险
传输我们相信,我们的数据将有助于为正在接受治疗的个人制定策略。
性别确认激素治疗,以减少艾滋病毒和其他性病的风险收购通过这一粘膜表面。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Robin R Ingalls其他文献
Robin R Ingalls的其他文献
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{{ item.author }}
{{ truncateString('Robin R Ingalls', 18)}}的其他基金
Role of Chlamydia Species in Preterm Birth and Placental Dysfunction
衣原体种类在早产和胎盘功能障碍中的作用
- 批准号:
8355427 - 财政年份:2012
- 资助金额:
$ 26.7万 - 项目类别:
Role of Chlamydia Species in Preterm Birth and Placental Dysfunction
衣原体种类在早产和胎盘功能障碍中的作用
- 批准号:
8500187 - 财政年份:2012
- 资助金额:
$ 26.7万 - 项目类别:
Role of Chlamydia Species in Preterm Birth and Placental Dysfunction
衣原体种类在早产和胎盘功能障碍中的作用
- 批准号:
8724108 - 财政年份:2012
- 资助金额:
$ 26.7万 - 项目类别:
Role of Chlamydia Species in Preterm Birth and Placental Dysfunction
衣原体种类在早产和胎盘功能障碍中的作用
- 批准号:
8681353 - 财政年份:2012
- 资助金额:
$ 26.7万 - 项目类别:
Defenses against Acute Chronic Infection with C pneumoniae
防御肺炎衣原体急性慢性感染
- 批准号:
7790031 - 财政年份:2010
- 资助金额:
$ 26.7万 - 项目类别:
Genetic variations in the innate immune response to Neisseria
对奈瑟菌的先天免疫反应的遗传变异
- 批准号:
7764289 - 财政年份:2009
- 资助金额:
$ 26.7万 - 项目类别:
Interaction of Chalmydia with Innate Immune Receptors
衣原体与先天免疫受体的相互作用
- 批准号:
7031654 - 财政年份:2005
- 资助金额:
$ 26.7万 - 项目类别:
Interaction of Chalmydia with Innate Immune Receptors
衣原体与先天免疫受体的相互作用
- 批准号:
7587338 - 财政年份:2005
- 资助金额:
$ 26.7万 - 项目类别:
Interaction of Chalmydia with Innate Immune Receptors
衣原体与先天免疫受体的相互作用
- 批准号:
7389550 - 财政年份:2005
- 资助金额:
$ 26.7万 - 项目类别:
Interaction of Chlamydia with Innate Immune Receptors
衣原体与先天免疫受体的相互作用
- 批准号:
6907637 - 财政年份:2005
- 资助金额:
$ 26.7万 - 项目类别:
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