JID innovations : skin science from molecules to population health最新文献_第5页

Superior Antiproliferative and Enhanced Synergistic Effects of a ROCK Inhibitor in Multiple Models for Keloid Disease 一种ROCK抑制剂在多种瘢痕疙瘩疾病模型中具有卓越的抗增殖和增强的协同作用

JID innovations : skin science from molecules to population health

Pub Date : 2025-07-30 DOI: 10.1016/j.xjidi.2025.100402

Zeinab Ghasemishahrestani , Traci A. Wilgus , Nonhlanhla P. Khumalo , Ardeshir Bayat

Keloid disease is a common fibroproliferative skin disorder characterized by excessive scar tissue formation and frequent recurrence. Limited therapies and study models hinder progress in addressing this unmet clinical need. AMA0825, a ROCK (Rho-associated protein kinase) inhibitor, has shown promising antifibrotic and antiproliferative effects in other fibrotic conditions. This study investigated the therapeutic potential of AMA0825 using in vitro, ex vivo, and a 3-dimensional spheroid model of keloid disease, which partially reflects features of the keloid microenvironment. AMA0825 demonstrated potent antiproliferative activity against keloid fibroblasts, with a half-maximal growth inhibitory concentration of 28.19 ± 1.6 nM, significantly outperforming dexamethasone (half-maximal growth inhibitory concentration = 35.35 ± 2.6 μM) and triamcinolone (half-maximal growth inhibitory concentration = 37.84 ± 3 μM). This effect was confirmed by decreased Ki-67 expression and cell cycle arrest at the G1 phase. In the 3-dimensional spheroid model, AMA0825 effectively inhibited cell proliferation at nanomolar concentrations, exceeding the efficacy of dexamethasone. Although AMA0825 did not demonstrate significant antifibrotic activity at lower concentrations, it exhibited antifibrotic effects at higher concentrations. In addition, synergistic effects were observed when combined with dexamethasone. This study highlights the potential of ROCK inhibitors, particularly AMA0825, as an antiproliferative agent for keloid disease and underscores the value of 3-dimensional spheroid models for evaluating alternative therapeutic strategies.

瘢痕疙瘩病是一种常见的纤维增生性皮肤疾病，其特征是瘢痕组织形成过多且经常复发。有限的治疗方法和研究模式阻碍了解决这一未满足的临床需求的进展。AMA0825是一种ROCK （rho相关蛋白激酶）抑制剂，在其他纤维化疾病中显示出有希望的抗纤维化和抗增殖作用。本研究通过体外、离体和瘢痕疙瘩病的三维球体模型来研究AMA0825的治疗潜力，该模型部分反映了瘢痕疙瘩微环境的特点。AMA0825对瘢痕疙瘩成纤维细胞表现出较强的抗增殖活性，半最大生长抑制浓度为28.19±1.6 nM，显著优于地塞米松（半最大生长抑制浓度为35.35±2.6 μM）和曲安奈德酮（半最大生长抑制浓度为37.84±3 μM）。Ki-67表达减少和细胞周期阻滞在G1期证实了这种作用。在三维球体模型中，AMA0825在纳摩尔浓度下有效抑制细胞增殖，超过地塞米松的效果。虽然AMA0825在低浓度下没有表现出明显的抗纤维化活性，但在高浓度下表现出抗纤维化作用。此外，与地塞米松合用可观察到协同效应。本研究强调了ROCK抑制剂，特别是AMA0825，作为瘢痕疙瘩疾病的抗增殖药物的潜力，并强调了三维球体模型在评估替代治疗策略方面的价值。

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引用次数: 0

Immunoregulatory Microenvironment in the Elderly Skin 老年皮肤的免疫调节微环境

JID innovations : skin science from molecules to population health

Pub Date : 2025-07-22 DOI: 10.1016/j.xjidi.2025.100401

Yuri Shimizu , Hanako Koguchi-Yoshioka , Toshiki Kubo , Yutaka Matsumura , Shoichi Matsuda , Atsushi Tanemura , Michiko Nomori , Naoya Otani , Mifue Taminato , Koichi Tomita , Tateki Kubo , Manabu Fujimoto , Rei Watanabe

Previous studies have revealed that skin T cells accumulate and maintain immune responses in the elderly. However, we questioned why these functional T cells fail to recognize and eliminate malignant cells, making elderly skin more prone to developing malignant tumors. To address this question, we examined the overall skin microenvironment in aging using the Nanostring nCounter system and 10x Xenium digital spatial RNA sequencing. The digital RNA counts of CIITA and HLA-DMA, which are involved in antigen presentation, were negatively correlated with age, whereas the counts of UBE2L3 and SOCS1, molecules that play roles in immune regulation, were positively correlated with aging. The upregulation of SOCS1 was detected in the microenvironment of the skin malignant tumors. Spatial transcriptome analysis revealed that cells with high levels of SOCS1 were distributed in upper dermis and periadnexal area, and some SOCS1-positive fibroblasts were closely lined with CD163-positive macrophages. Our study showed that the skin microenvironment in the elderly may shift to an immunoregulatory condition. Furthermore, modulating certain molecules that may be involved in shared immunoregulatory mechanisms between healthy elderly skin and malignant tumors could serve as a potential strategy for preventing malignancies in elderly skin.

先前的研究表明，皮肤T细胞在老年人中积累并维持免疫反应。然而，我们质疑为什么这些功能性T细胞不能识别和消除恶性细胞，使老年皮肤更容易发生恶性肿瘤。为了解决这个问题，我们使用Nanostring nCounter系统和10x Xenium数字空间RNA测序检测了衰老过程中的整体皮肤微环境。参与抗原呈递的CIITA和HLA-DMA的数字RNA计数与年龄呈负相关，而参与免疫调节的UBE2L3和SOCS1的数字RNA计数与年龄呈正相关。在皮肤恶性肿瘤的微环境中检测到SOCS1的上调。空间转录组分析显示，高水平的SOCS1细胞分布在真皮上部和附件周围区域，部分SOCS1阳性的成纤维细胞与cd163阳性的巨噬细胞紧密排列。我们的研究表明，老年人的皮肤微环境可能转变为免疫调节状态。此外，调节某些可能参与健康老年皮肤和恶性肿瘤之间共享免疫调节机制的分子可能作为预防老年皮肤恶性肿瘤的潜在策略。

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引用次数: 0

Characterization of Malignant Adnexal Tumors of the Head and Neck by Targeted Analysis of Cancer Genes and Human Papillomavirus 42 肿瘤基因和人乳头瘤病毒靶向分析头颈部附件恶性肿瘤的特征

JID innovations : skin science from molecules to population health

Pub Date : 2025-07-07 DOI: 10.1016/j.xjidi.2025.100398

Eleanor Dowell , Ruchika Mahapatra , Justin Bishop , Andrew Matsumoto , Alexandra Callan , Travis W. Vandergriff , Aya Alame , Greg Hosler , Jeffrey Gagan , Rajiv I. Nijhawan , Richard C. Wang

Malignant adnexal tumors of the head and neck, including syringoid eccrine carcinoma and microcystic adnexal carcinoma, are rare tumors that are thought to arise in adnexal epithelium. The etiopathogenesis of these tumors is poorly understood, and the precise classification of these tumors can be challenging. Human papillomavirus 42 (HPV42) promotes the development of digital papillary adenocarcinoma, a rare adnexal tumor of the extremities and genital skin. Malignant adnexal tumors of the head and neck were assessed through targeted RNA sequencing of the cancer exome and specific RT-PCR for HPV42. Of the 9 cases identified, 7 yielded RNA of sufficient quality for RNA sequencing. Unexpectedly, these analyses revealed a MYB::NFIB fusion in 1 case, suggesting a molecular diagnosis of adenoid cystic carcinoma. Mutations in TP53 were identified in 2 cases, and a missense mutation in Jak1 (p.Ser914Asn) was identified in 1 case. For the 6 cases with sufficient RNA, transcripts for the early region of HPV42 could not be identified by RT-PCR. In situ hybridization and RT-PCR confirmed the presence of HPV42 in digital papillary adenocarcinoma. Our study confirms the presence of mutations in TP53 and Jak1 and suggests that HPV42 does not contribute to malignant adnexal tumors of the head and neck.

头颈部的恶性附件肿瘤，包括腺样腺癌和微囊性附件癌，是罕见的肿瘤，被认为起源于附件上皮。这些肿瘤的发病机制尚不清楚，对这些肿瘤的精确分类可能具有挑战性。人乳头瘤病毒42 （HPV42）促进数字乳头状腺癌的发展，这是一种罕见的四肢和生殖器皮肤的附件肿瘤。通过肿瘤外显子组靶向RNA测序和HPV42特异性RT-PCR对头颈部附件恶性肿瘤进行评估。在鉴定的9例病例中，7例产生了足够质量的RNA进行RNA测序。出乎意料的是，这些分析在1例中发现MYB::NFIB融合，提示腺样囊性癌的分子诊断。2例发现TP53突变，1例发现Jak1错义突变（p.Ser914Asn）。在RNA充足的6例病例中，RT-PCR无法鉴定HPV42早期区域的转录本。原位杂交和RT-PCR证实了HPV42在指状腺癌中的存在。我们的研究证实了TP53和Jak1突变的存在，并表明HPV42不会导致头颈部的恶性附件肿瘤。

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引用次数: 0

Divergence in Estimated Risks and Actual Rates of Atherosclerotic Cardiovascular Events and their Management in a Longitudinal Cohort of Patients with Dermatomyositis with Skin Involvement 一项累及皮肤的皮肌炎患者纵向队列中动脉粥样硬化性心血管事件的估计风险和实际发生率及其管理的差异

JID innovations : skin science from molecules to population health

Pub Date : 2025-07-07 DOI: 10.1016/j.xjidi.2025.100399

Megan Zhao , Caroline Stone , Rui Feng , Victoria P. Werth , Kevin Jon Williams

Patients with dermatomyositis (DM), an autoimmune disorder affecting the skin, muscle, and lung, have been reported to be at a heightened risk of clinical events, chiefly heart attacks and strokes, from atherosclerotic cardiovascular disease. In this study, we examined current cardiovascular management in a single-center study of all 388 patients who have DM with skin involvement, either with symptomatic muscle disease (“classic DM”) or with clinically amyopathic DM. By the new guidelines, the most recent low-density lipoprotein cholesterol levels were above goal for 290 of 388 (74.7%). Surprisingly, statin use was similar between this cohort and a longitudinal lupus cohort. Almost two thirds of the cohort had hypertension (249 of 388, 64.2%), which was undertreated or untreated in 199 of 249 (79.9%). One third of the cohort were former or current smokers. Prediabetes and diabetes were generally well-managed. Three published methods for estimating atherosclerotic cardiovascular disease event risk in primary prevention showed meaningful discordance for 196 of 305 (64.3%). The documented rate of atherosclerotic cardiovascular disease events in the first 10 years after enrollment was 12.8% for classic DM and 8.4% for clinically amyopathic DM, indicating at-risk populations. We conclude that patients with DM are undermanaged for conventional therapeutic targets to reduce atherosclerotic cardiovascular disease event risk, particularly hypercholesteremia and hypertension.

皮肌炎（DM）是一种影响皮肤、肌肉和肺部的自身免疫性疾病，据报道，皮肌炎患者有较高的临床事件风险，主要是由动脉粥样硬化性心血管疾病引起的心脏病发作和中风。在这项研究中，我们对388例伴有皮肤病变的糖尿病患者进行了一项单中心研究，检查了目前的心血管管理情况，这些患者要么有症状性肌肉疾病（“典型糖尿病”），要么有临床淀粉性糖尿病。根据新的指南，388例患者中，最近的低密度脂蛋白胆固醇水平高于目标水平的有290例（74.7%）。令人惊讶的是，他汀类药物的使用在这个队列和一个纵向狼疮队列之间是相似的。几乎三分之二的队列患者患有高血压（388人中有249人，64.2%），249人中有199人（79.9%）治疗不足或未治疗。三分之一的研究对象曾经或现在是吸烟者。糖尿病前期和糖尿病一般都得到了很好的管理。三种已发表的评估初级预防中动脉粥样硬化性心血管疾病事件风险的方法在305例中有196例（64.3%）显示有意义的不一致。在入组后的前10年，记录在案的动脉粥样硬化性心血管疾病事件发生率，典型糖尿病为12.8%，临床淀粉性糖尿病为8.4%，表明存在高危人群。我们得出结论，糖尿病患者在降低动脉粥样硬化性心血管疾病事件风险的常规治疗目标方面管理不足，特别是高胆固醇血症和高血压。

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引用次数: 0

Assessment of Primary Malignancy Risk after Initiation of Biologic Therapy in Patients with Psoriasis 银屑病患者开始生物治疗后原发性恶性肿瘤风险的评估

JID innovations : skin science from molecules to population health

Pub Date : 2025-07-04 DOI: 10.1016/j.xjidi.2025.100397

Chunghwan Ro , Ana Ormaza Vera , Waleed Adawi , Alexander Yap , Clinton W. Enos

Limited evidence exists regarding the long-term oncologic safety of biologic therapies, particularly IL-17 inhibitors and IL-23 inhibitors, in the management of psoriasis. This propensity score–matched retrospective cohort study assessed the risk of developing a primary malignancy within 10 years after exposure to a Food and Drug Administration–approved biologic among patients with psoriasis compared with that among biologic-naïve controls. After propensity score matching, 32,230 biologic-exposed patients were further grouped into cohorts of TNF inhibitors (n = 16,011), IL-23 inhibitors (n = 5604), IL-12/23 inhibitors (n =3856), and IL-17 inhibitors (n = 5467). During a 10-year period, TNF inhibitor–treated patients had a reduced risk of developing any primary malignancy compared with biologic-naïve patients with psoriasis (hazard ratio [HR] = 0.80; 95% confidence interval [CI] = 0.73–0.87). Similarly, a lower incidence of any malignancy was observed among patients on IL-23 inhibitors (HR = 0.83; 95% CI = 0.68–1.02), IL-12/23 inhibitors (HR = 0.85; 95% CI = 0.71–1.03), or IL-17 inhibitors (HR = 0.87; 95% CI = 0.73–1.04); however, the differences did not reach statistical significance. TNF inhibitor users were less likely to develop nonmelanoma skin cancer (HR = 0.82; 95% CI = 0.71–0.96) than controls, and the risk of nonmelanoma skin cancer did not significantly differ among users of IL-23 inhibitors (HR = 1.09; 95% CI = 0.77–1.55), IL-12/23 inhibitors (HR = 1.22; 95% CI = 0.90–1.64), or IL-17 inhibitors (HR = 1.03; 95% CI = 0.77–1.38). Exposure to any biologic class did not associate with the risk of developing melanoma or lymphoid/hematopoietic malignancies. Overall, these results provide evidence for the long-term oncologic safety of biologic therapies in the management of psoriasis.

关于生物疗法，特别是IL-17抑制剂和IL-23抑制剂治疗银屑病的长期肿瘤学安全性的证据有限。这项倾向评分匹配的回顾性队列研究评估了银屑病患者暴露于食品和药物管理局批准的生物制剂后10年内发生原发性恶性肿瘤的风险，并与biologic-naïve对照组进行了比较。在倾向评分匹配后，32,230名生物暴露患者被进一步分组为TNF抑制剂（n = 16,011）， IL-23抑制剂（n = 5604）， IL-12/23抑制剂（n =3856）和IL-17抑制剂（n = 5467）。在10年期间，与biologic-naïve银屑病患者相比，TNF抑制剂治疗的患者发生任何原发性恶性肿瘤的风险降低(风险比[HR] = 0.80；95%置信区间[CI] = 0.73-0.87)。同样，在使用IL-23抑制剂的患者中，任何恶性肿瘤的发生率都较低(HR = 0.83；95% CI = 0.68-1.02)， IL-12/23抑制剂(HR = 0.85；95% CI = 0.71-1.03)或IL-17抑制剂(HR = 0.87；95% ci = 0.73-1.04)；但差异无统计学意义。TNF抑制剂使用者发生非黑色素瘤皮肤癌的可能性较低(HR = 0.82；95% CI = 0.71-0.96)，非黑色素瘤皮肤癌的风险在使用IL-23抑制剂的人群中没有显著差异(HR = 1.09；95% CI = 0.77-1.55)， IL-12/23抑制剂(HR = 1.22；95% CI = 0.90-1.64)或IL-17抑制剂(HR = 1.03；95% ci = 0.77-1.38)。暴露于任何生物类与发生黑色素瘤或淋巴/造血恶性肿瘤的风险无关。总之，这些结果为银屑病生物治疗的长期肿瘤学安全性提供了证据。

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引用次数: 0

Cover 封面

JID innovations : skin science from molecules to population health

Pub Date : 2025-07-01 DOI: 10.1016/S2667-0267(25)00051-7

引用次数: 0

Identification of Keratin 5-Expressing Fibroblasts for Regenerating Keratinocytes in the Necrotic Skin Graft 表达角蛋白5的成纤维细胞在坏死皮肤移植中再生角化细胞的鉴定

JID innovations : skin science from molecules to population health

Pub Date : 2025-07-01 DOI: 10.1016/j.xjidi.2025.100394

Yoshikazu Hirose , Asaka Miura , Yuki Kobayashi , Takashi Shimbo , Yuya Ouchi , Tomomi Kitayama , Tomoya Mori , Akio Tanaka , Manabu Fujimoto , Kotaro Saga , Katsuto Tamai

Skin transplantation is commonly used to compensate for normal cutaneous tissues in full-thickness wounds or surgically excised skin. Despite complete termination of initial blood flow, transplanted skin usually maintains its dermal and epidermal structures without scar formation. However, the precise role of engrafted cells in maintaining epidermal and dermal homeostasis remains unclear. In this study, we investigated the chronological changes in neonatal full-thickness skin grafts on mice at the histological and single-cell transcriptomic levels. We found devastating necrotic changes in the dermal and epidermal tissues on postoperative day 3, followed by significant regeneration of follicular and interfollicular tissues after postoperative day 6. We identified a unique mesenchymal subpopulation that expressed keratinocyte-specific genes (keratin 5 gene Krt5, Epcam, and Irf6) involved in mesenchymal–epithelial transition. Mesenchymal cells transitioning to epithelial cells showed keratinocyte differentiation activity both in vitro and in vivo. These results highlight the contribution of unique mesenchymal cell populations to epithelial regeneration after severe necrosis of a skin graft.

皮肤移植通常用于补偿全层伤口或手术切除皮肤的正常皮肤组织。尽管最初的血流完全终止，移植的皮肤通常保持其真皮和表皮结构而不形成疤痕。然而，移植细胞在维持表皮和真皮稳态中的确切作用尚不清楚。在这项研究中，我们在组织学和单细胞转录组水平上研究了新生小鼠全层皮肤移植物的时间变化。术后第3天，我们发现真皮和表皮组织发生了毁灭性的坏死变化，术后第6天，毛囊和毛囊间组织出现了明显的再生。我们发现了一个独特的间充质亚群，表达角朊细胞特异性基因（角蛋白5基因Krt5、Epcam和Irf6），参与间充质-上皮转化。在体内和体外，间充质细胞向上皮细胞转化均表现出角质细胞分化活性。这些结果突出了独特的间充质细胞群对皮肤移植严重坏死后上皮细胞再生的贡献。

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引用次数: 0

Accounting for Biological Sex and Gender Identity in the Pathogenesis, Artistic Depictions, and Quality of Life in Neurofibromatosis Type 1 1型神经纤维瘤病发病机制、艺术表现和生活质量中的生理性别和性别认同

JID innovations : skin science from molecules to population health

Pub Date : 2025-06-25 DOI: 10.1016/j.xjidi.2025.100393

Nidhi Kuchimanchi , Renee M. McKay , Lu Q. Le

Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous syndrome caused by pathogenic alterations in the tumor suppressor protein neurofibromin. NF1 is characterized clinically by café-au-lait macules, skinfold freckling, iris hamartomas, benign and malignant nerve sheath tumors, optic pathway tumors, skeletal abnormalities, breast malignancies, and neurocognitive challenges. Although progress has been made in understanding biological sex- and gender identity–based differences in a variety of dermatologic conditions, the role of these factors on NF1 and vice versa is not well-defined. In this narrative review, we examine the reciprocal influences of biological sex and gender identity on various NF1 clinical features, discuss the psychosocial and sociocultural factors that may contribute to these observed effects, and highlight historical artistic depictions of NF1. We also identify gaps in our current knowledge in this area that warrant additional research. A comprehensive understanding of NF1 clinical presentations through the lens of biological sex and gender identity can lead to a patient-centered approach of treatment, thereby improving long-term outcomes for affected patients.

1型神经纤维瘤病（NF1）是一种常染色体显性神经皮肤综合征，由肿瘤抑制蛋白神经纤维蛋白的致病性改变引起。NF1的临床特征为卡萨梅-奥-lait斑疹、皮褶雀斑、虹膜错构瘤、良恶性神经鞘肿瘤、视神经通路肿瘤、骨骼异常、乳腺恶性肿瘤和神经认知挑战。尽管在了解各种皮肤病中基于生理性别和性别认同的差异方面取得了进展，但这些因素对NF1的作用并没有明确定义，反之亦然。在这篇叙述性综述中，我们研究了生理性别和性别认同对NF1各种临床特征的相互影响，讨论了可能导致这些观察到的影响的心理社会和社会文化因素，并强调了NF1的历史艺术描述。我们还确定了我们目前在这一领域的知识差距，需要进一步的研究。从生理性别和性别认同的角度全面了解NF1的临床表现，可以引导以患者为中心的治疗方法，从而改善受影响患者的长期预后。

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引用次数: 0

Myeloid and Mast Cell Progenitors Are Elevated in Atopic Dermatitis 髓系和肥大细胞祖细胞在特应性皮炎中升高

JID innovations : skin science from molecules to population health

Pub Date : 2025-06-20 DOI: 10.1016/j.xjidi.2025.100390

Katie Ridge , Barry Moran , Mark A. Little , Cliona O’Farrelly , Jean Dunne , Julianne Clowry , Clodagh Loftus , Conor M. Finlay , Alan D. Irvine , Niall Conlon

Chronic spontaneous urticaria and atopic dermatitis (AD) are chronic skin disorders characterized by itch. Although mast cells play an integral role in the pathogenesis of chronic spontaneous urticaria, their role in AD is unclear, having a contributory role in a disease largely driven by T helper 2 polarization. Despite this, the role of mast cells in AD is important, given their release of proinflammatory mediators. Recently, myeloid and mast cell progenitors were identified as potential biomarkers for treatment response in chronic spontaneous urticaria. These Lin⁻CD117⁺CD34⁺FceRI⁺ cells appear to have increased egress from the bone marrow in atopy. We measured Lin⁻CD117⁺CD34⁺FceRI⁺ cells in the peripheral blood of 10 individuals with AD and 10 healthy controls. Flow cytometry revealed a significant increase in myeloid progenitors in participants with AD (P = .0067). Total serum IgE levels did not correlate with myeloid progenitors. To our knowledge, examination of this cell type in AD is previously unreported. Our findings suggest increased progenitor egress from the bone marrow in these patients and a possible role for myeloid progenitors in disease pathogenesis.

慢性自发性荨麻疹和特应性皮炎（AD）是一种以瘙痒为特征的慢性皮肤病。尽管肥大细胞在慢性自发性荨麻疹的发病机制中起着不可或缺的作用，但它们在AD中的作用尚不清楚，在很大程度上由辅助性T 2极化驱动的疾病中起着促进作用。尽管如此，肥大细胞在AD中的作用是重要的，因为它们释放促炎介质。最近，骨髓和肥大细胞祖细胞被确定为慢性自发性荨麻疹治疗反应的潜在生物标志物。这些Lin - CD117+CD34+FceRI+细胞似乎在特应性中增加了从骨髓的输出。我们测量了10名AD患者和10名健康对照者外周血中的Lin - CD117+CD34+FceRI+细胞。流式细胞术显示AD患者髓系祖细胞显著增加（P = 0.0067）。血清总IgE水平与髓系祖细胞无相关性。据我们所知，在阿尔茨海默病中对这种细胞类型的检查以前没有报道。我们的研究结果表明，这些患者骨髓中祖细胞的分泌增加，骨髓祖细胞可能在疾病发病机制中发挥作用。

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引用次数: 0

Sex Bias in Autoimmunity: New Findings and New Opportunities 自身免疫中的性别偏见：新发现和新机遇

JID innovations : skin science from molecules to population health

Pub Date : 2025-06-20 DOI: 10.1016/j.xjidi.2025.100391

Vincent van Drongelen , Joanna Rew , Allison C. Billi

Autoimmune diseases result from the immune system’s inability to discriminate between self and foreign antigens, leading to development of self-reactive immune cells and autoantibodies that can cause organ damage and failure. It has long been known that many autoimmune diseases are more common in females. Although much progress has been made over the years, the exact mechanisms for this sex bias are not yet fully understood. In this review, we provide an overview and update on how chromosomes, genes, sex hormones (including gender-affirming hormone therapy), immunometabolism, and the skin can play a role in sex-biased autoimmunity. We also identify gaps in our understanding that require additional research. In an era of increased development of personalized medicine, a thorough understanding of sex bias in autoimmunity may facilitate the development of much-needed targeted therapeutics, thereby reducing the risks of broader immunosuppression and adverse effects that lead to premature termination of treatment by patients.

自身免疫性疾病是由于免疫系统无法区分自身和外来抗原，导致自身反应性免疫细胞和自身抗体的发展，从而导致器官损伤和衰竭。人们早就知道，许多自身免疫性疾病在女性中更为常见。尽管多年来已经取得了很大的进展，但这种性别偏见的确切机制还没有被完全理解。在这篇综述中，我们提供了染色体、基因、性激素（包括性别确认激素治疗）、免疫代谢和皮肤如何在性别偏向性自身免疫中发挥作用的概述和最新进展。我们还发现了需要进一步研究的理解差距。在个性化医疗日益发展的时代，彻底了解自身免疫中的性别偏见可能有助于开发急需的靶向治疗方法，从而降低导致患者过早终止治疗的广泛免疫抑制和不良反应的风险。

引用次数: 0