Among transgender women (TGW), the effects of feminizing hormone therapy use on rectal mucosal (RM) HIV transmission are largely unknown. In this small pilot study, we compared the RM transcriptome in TGW utilizing feminizing hormone therapy with a group of cisgender men who have sex with men (MSM) engaging in condomless receptive anal intercourse (AI) and to a group of cisgender men who had never engaged in AI. There were 498 differentially expressed genes (DEGs) in TGW compared with men who had never engaged in AI, and 154 DEGs compared with the MSM. Among TGW, a unique RM transcriptome was identified that implicated pathways critical for mucosal immune responses, including upregulation of genes that mediate immune cell activation and the production of cytokines and other immune signaling molecules. Furthermore, gene set enrichment analyses identified immune signatures that implicated enrichment of proinflammatory immunological pathways in TGW, specifically involving interferon-α, interleukin-6, and tumor necrosis factor-α signaling, whereas metabolic pathways were shown to be enriched among the cisgender male groups. These findings suggest that TGW have a distinct RM immune environment influenced by the use of feminizing hormones, and consequently, there is an urgent need for further investigation into the immunological effects of gender-affirming hormone therapy and its potential impact on HIV mucosal transmission risk for transgender individuals.

中文翻译：

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简短交流：接受女性化激素治疗的跨性别女性展示了来自顺性别男性的独特直肠粘膜转录组。

在跨性别女性 (TGW) 中，使用女性化激素疗法对直肠粘膜 (RM) HIV 传播的影响在很大程度上是未知的。在这项小型试点研究中，我们将使用女性化激素疗法的 TGW 中的 RM 转录组与一组从事无安全套接受肛交 (AI) 的男男性行为 (MSM) 和一组从未接受过性交的顺性别男性进行了比较。从事人工智能。与从未参与 AI 的男性相比，TGW 中有 498 个差异表达基因（DEG），与 MSM 相比有 154 个差异表达基因。在 TGW 中，发现了一个独特的 RM 转录组，它涉及粘膜免疫反应的关键途径，包括介导免疫细胞活化的基因的上调以及细胞因子和其他免疫信号分子的产生。此外，基因集富集分析确定了与 TGW 中促炎免疫通路富集有关的免疫特征，特别是涉及干扰素-α、白细胞介素-6 和肿瘤坏死因子-α 信号传导，而代谢通路显示在顺性别男性群体中富集。这些发现表明，TGW 具有受女性化激素使用影响的独特 RM 免疫环境，因此，迫切需要进一步研究性别肯定激素疗法的免疫学效应及其对 HIV 粘膜传播风险的潜在影响。变性人。而代谢途径被证明在顺性别男性群体中更为丰富。这些发现表明，TGW 具有受女性化激素使用影响的独特 RM 免疫环境，因此，迫切需要进一步研究性别肯定激素疗法的免疫学效应及其对 HIV 粘膜传播风险的潜在影响。变性人。而代谢途径被证明在顺性别男性群体中更为丰富。这些发现表明，TGW 具有受女性化激素使用影响的独特 RM 免疫环境，因此，迫切需要进一步研究性别肯定激素疗法的免疫学效应及其对 HIV 粘膜传播风险的潜在影响。变性人。