首页 > 最新文献

The Journal of investigative dermatology最新文献

英文 中文
SOX2-Dependent Wound Repair Signature Triggers Prohealing Outcome in Hyperglycemic Wounds. 依赖于 SOX2 的伤口修复特征可促进高血糖伤口的愈合。
Pub Date : 2024-08-08 DOI: 10.1016/j.jid.2024.07.012
Christopher G O'Neill, Andrew P Sawaya, Spencer Mehdizadeh, Stephen R Brooks, Kowser Hasneen, Subhashree Nayak, Andrew M Overmiller, Maria I Morasso
{"title":"SOX2-Dependent Wound Repair Signature Triggers Prohealing Outcome in Hyperglycemic Wounds.","authors":"Christopher G O'Neill, Andrew P Sawaya, Spencer Mehdizadeh, Stephen R Brooks, Kowser Hasneen, Subhashree Nayak, Andrew M Overmiller, Maria I Morasso","doi":"10.1016/j.jid.2024.07.012","DOIUrl":"10.1016/j.jid.2024.07.012","url":null,"abstract":"","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Single-cell Analysis of Debrided Diabetic Foot Ulcers Reveals Dysregulated Wound Healing Environment in non-Hispanic Blacks. 对去骨糖尿病足溃疡的单细胞分析揭示了非西班牙裔黑人的伤口愈合环境失调。
Pub Date : 2024-08-08 DOI: 10.1016/j.jid.2024.07.017
Dahim Choi, Mojtaba Bakhtiari, William Pilcher, Chenbin Huang, Beena E Thomas, Hope Mumme, Gerardo Blanco, Ravi Rajani, Marcos C Schechter, Maya Fayfman, Gabriel Santamarina, Swati Bhasin, Manoj Bhasin

Diabetic foot ulcer (DFU) is a critical complication of diabetes, but the wound microenvironment and its healing process are not completely understood. In this study, we optimized single-cell profiling from sharp debrided ulcers. Our findings demonstrate that healing-DFUs were significantly enriched with distinct fibroblasts expressing genes related to inflammation (CHI3L1, IL6) and extracellular matrix remodeling (ASPN), validating our previous studies on surgically resected ulcers. The race-focused analysis depicted lower expression of key healing-associated genes such as CHIL3L1, MMP11, and SFRP4 in fibroblasts of non-Hispanic Black (NHB) patients compared to White patients. In cellular communication analysis, healing enriched fibroblasts of NHBs exhibited upregulation of signaling pathways such as WNT while those of White showed IGF and MK pathways upregulation. Our findings advocate race as a risk marker of DFU outcomes, likely reflecting underlying disparities in environmental exposures and access to care that profoundly influence healing markers. Using sharp debrided tissues for single-cell assays, this study highlights the need for in-depth investigations into dysregulated wound healing microenvironments of under-represented racial groups.

糖尿病足溃疡(DFU)是糖尿病的一种严重并发症,但人们对伤口微环境及其愈合过程还不完全了解。在这项研究中,我们对锐器剥离溃疡的单细胞图谱进行了优化。我们的研究结果表明,愈合的DFU明显富集了表达炎症(CHI3L1、IL6)和细胞外基质重塑(ASPN)相关基因的成纤维细胞,这验证了我们之前对手术切除溃疡的研究结果。以种族为重点的分析显示,与白人患者相比,非西班牙裔黑人(NHB)患者成纤维细胞中与愈合相关的关键基因(如 CHIL3L1、MMP11 和 SFRP4)的表达量较低。在细胞通讯分析中,非西班牙裔黑人的愈伤富集成纤维细胞表现出信号通路(如 WNT)的上调,而白人的愈伤富集成纤维细胞则表现出 IGF 和 MK 通路的上调。我们的研究结果表明,种族是 DFU 结果的一个风险标志,可能反映了环境暴露和获得护理方面的潜在差异,这些差异对愈合标志物有深远影响。这项研究利用锐利的去骨组织进行单细胞检测,强调了对代表性不足的种族群体伤口愈合微环境失调进行深入研究的必要性。
{"title":"Single-cell Analysis of Debrided Diabetic Foot Ulcers Reveals Dysregulated Wound Healing Environment in non-Hispanic Blacks.","authors":"Dahim Choi, Mojtaba Bakhtiari, William Pilcher, Chenbin Huang, Beena E Thomas, Hope Mumme, Gerardo Blanco, Ravi Rajani, Marcos C Schechter, Maya Fayfman, Gabriel Santamarina, Swati Bhasin, Manoj Bhasin","doi":"10.1016/j.jid.2024.07.017","DOIUrl":"https://doi.org/10.1016/j.jid.2024.07.017","url":null,"abstract":"<p><p>Diabetic foot ulcer (DFU) is a critical complication of diabetes, but the wound microenvironment and its healing process are not completely understood. In this study, we optimized single-cell profiling from sharp debrided ulcers. Our findings demonstrate that healing-DFUs were significantly enriched with distinct fibroblasts expressing genes related to inflammation (CHI3L1, IL6) and extracellular matrix remodeling (ASPN), validating our previous studies on surgically resected ulcers. The race-focused analysis depicted lower expression of key healing-associated genes such as CHIL3L1, MMP11, and SFRP4 in fibroblasts of non-Hispanic Black (NHB) patients compared to White patients. In cellular communication analysis, healing enriched fibroblasts of NHBs exhibited upregulation of signaling pathways such as WNT while those of White showed IGF and MK pathways upregulation. Our findings advocate race as a risk marker of DFU outcomes, likely reflecting underlying disparities in environmental exposures and access to care that profoundly influence healing markers. Using sharp debrided tissues for single-cell assays, this study highlights the need for in-depth investigations into dysregulated wound healing microenvironments of under-represented racial groups.</p>","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
PCSK9 Inhibitors and the Risk of Vitiligo: A Mendelian Randomization Study. PCSK9抑制剂与白癜风风险:孟德尔随机研究。
Pub Date : 2024-08-08 DOI: 10.1016/j.jid.2024.07.021
Tae-Jong Kang, Sun Yeop Lee, Sanghyuk Yoon, Eun Gyo Kim, Jung Oh Kim, Jong-Seung Kim, Jin Park, Kyung-Hwa Nam

Lipid-lowering agents have been suggested as a therapeutic option for vitiligo on the basis of the potential pathogenic role of lipid metabolism abnormalities. We aimed to explore the impact of genetically proxied lipid-lowering agents on the risk of vitiligo and potentially associated mediators. GWAS summary statistics for European ancestry were extracted from the largest available meta-analysis for vitiligo: the Global Lipids Genetics Consortium for 7 lipid profiles and 2 large biobanks, UK Biobank and deCODE, for 4719 proteins. After identifying lipid-lowering agents with genetically proxied protective effects against vitiligo using lipid-lowering and protein-inhibition Mendelian randomization (MR) analyses, multivariable and 2-step MR analyses were conducted to identify potential mediators between lipid-lowering agents and vitiligo. Lipid-lowering MR indicated a potential role of PCSK9 in reducing the vitiligo risk (OR [95% confidence interval] = 0.71 [0.52-0.95]), which was replicated in PCSK9-inhibition MR analyses across 2 separate biobanks (UK Biobank: OR [95% confidence interval] = 0.82 [0.71-0.96]; deCODE: OR [95% confidence interval] = 0.78 [0.67-0.91]). Multivariable MR suggested that well-known lipid profiles do not mediate the relationship between PCSK9 and vitiligo, whereas 2-step MR analyses identified 5 potential protein mediators (CCN5, CXCL12, FCRL1, legumain, and FGF2). Hence, PCSK9 inhibitor may attenuate the vitiligo risk; PCSK9 and the potential protein mediators can serve as promising novel therapeutic targets for its effective treatment.

基于脂质代谢异常的潜在致病作用,降脂药被建议作为白癜风的一种治疗选择。我们的目的是探讨基因代降脂药对白癜风风险的影响以及潜在的相关介质。我们从现有最大的白癜风荟萃分析、全球血脂遗传学联合会(Global Lipids Genetics Consortium)的七种血脂谱以及两个大型生物库(UKB 和 deCODE)的 4,719 种蛋白质中提取了欧洲血统的全基因组关联研究汇总统计数据。在利用降脂和蛋白抑制孟德尔随机化(MR)分析确定了对白癜风具有基因保护作用的降脂药物后,又进行了多变量和两步MR分析,以确定降脂药物与白癜风之间的潜在介导因素。降脂MR表明PCSK9在降低白癜风风险中的潜在作用(OR[95%CI]=0.71[0.52-0.95]),这在两个独立生物库的PCSK9抑制MR分析中得到了重复(UKB:OR[95%CI]=0.82[0.71-0.96];deCODE:OR[95%CI]=0.78[0.67-0.91])。多变量磁共振分析表明,众所周知的脂质特征并不介导 PCSK9 与白癜风之间的关系,而两步磁共振分析确定了五个潜在的蛋白质介导因子(CCN5、CXCL12、FCRL1、LGMN 和 FGF2)。因此,PCSK9抑制剂可能会降低白癜风风险;PCSK9和潜在的蛋白介质可作为有效治疗白癜风的新型治疗靶点。
{"title":"PCSK9 Inhibitors and the Risk of Vitiligo: A Mendelian Randomization Study.","authors":"Tae-Jong Kang, Sun Yeop Lee, Sanghyuk Yoon, Eun Gyo Kim, Jung Oh Kim, Jong-Seung Kim, Jin Park, Kyung-Hwa Nam","doi":"10.1016/j.jid.2024.07.021","DOIUrl":"10.1016/j.jid.2024.07.021","url":null,"abstract":"<p><p>Lipid-lowering agents have been suggested as a therapeutic option for vitiligo on the basis of the potential pathogenic role of lipid metabolism abnormalities. We aimed to explore the impact of genetically proxied lipid-lowering agents on the risk of vitiligo and potentially associated mediators. GWAS summary statistics for European ancestry were extracted from the largest available meta-analysis for vitiligo: the Global Lipids Genetics Consortium for 7 lipid profiles and 2 large biobanks, UK Biobank and deCODE, for 4719 proteins. After identifying lipid-lowering agents with genetically proxied protective effects against vitiligo using lipid-lowering and protein-inhibition Mendelian randomization (MR) analyses, multivariable and 2-step MR analyses were conducted to identify potential mediators between lipid-lowering agents and vitiligo. Lipid-lowering MR indicated a potential role of PCSK9 in reducing the vitiligo risk (OR [95% confidence interval] = 0.71 [0.52-0.95]), which was replicated in PCSK9-inhibition MR analyses across 2 separate biobanks (UK Biobank: OR [95% confidence interval] = 0.82 [0.71-0.96]; deCODE: OR [95% confidence interval] = 0.78 [0.67-0.91]). Multivariable MR suggested that well-known lipid profiles do not mediate the relationship between PCSK9 and vitiligo, whereas 2-step MR analyses identified 5 potential protein mediators (CCN5, CXCL12, FCRL1, legumain, and FGF2). Hence, PCSK9 inhibitor may attenuate the vitiligo risk; PCSK9 and the potential protein mediators can serve as promising novel therapeutic targets for its effective treatment.</p>","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Subcellular Fractionation and Metaproteogenomic Identification and Validation of Key Differentially Expressed Molecular Targets for Keloid Disease. 亚细胞分馏和元蛋白基因组学鉴定及验证瘢痕疙瘩病的关键差异表达分子靶标
Pub Date : 2024-08-07 DOI: 10.1016/j.jid.2024.07.010
Elvis B Kidzeru, Musalula Sinkala, Temwani Chalwa, Relebohile Matobole, Madeha Alkelani, Zeinab Ghasemishahrestani, Stanley K Mbandi, Jonathan Blackburn, David L Tabb, Henry Ademola Adeola, Nonhlanhla P Khumalo, Ardeshir Bayat

Keloid disease (KD) is a common connective tissue disorder of unknown aetiopathogenesis with ill-defined treatment. Keloid scars present as exophytic fibroproliferative reticular lesions postcutaneous injury, and even though KD remains neoplastically benign, keloid lesions behave locally aggressive, invasive and expansive. To date, there is limited understanding and validation of biomarkers identified through combined proteomic and genomic evaluation of KD. Therefore, the aim in this study was to identify putative causative candidates in KD by performing a comprehensive proteomics analysis of subcellular fractions as well as the whole cell, coupled with transcriptomics data analysis of normal compared with KD fibroblasts. We then applied novel integrative bioinformatics analysis to demonstrate that NF-kB-p65 (RELA) from the cytosolic fraction and CAPN2 from the whole-cell lysate were statistically significantly upregulated in KD and associated with alterations in relevant key signaling pathways, including apoptosis. Our findings were further confirmed by showing upregulation of both RELA and CAPN2 in KD using flow cytometry and immunohistochemistry. Moreover, functional evaluation using real-time cell analysis and flow cytometry demonstrated that both omeprazole and dexamethasone inhibited the growth of KD fibroblasts by enhancing the rate of apoptosis. In conclusion, subcellular fractionation and metaproteogenomic analyses have identified, to our knowledge, 2 previously unreported biomarkers of significant relevance to keloid diagnostics and therapeutics.

瘢痕疙瘩病(KD)是一种常见的结缔组织疾病,发病机制不明,治疗方法也不明确。瘢痕疙瘩在皮肤损伤后表现为外生性纤维增生性网状病变,仍为良性,但具有局部侵袭性和扩张性。迄今为止,人们对瘢痕疙瘩的蛋白质组和基因组联合评估所确定的生物标志物的了解和验证还很有限。因此,本文旨在通过对亚细胞组分和整个细胞进行全面的蛋白质组学分析,并结合对正常成纤维细胞和KD成纤维细胞的转录组学数据分析,确定KD的推定致病候选因子。然后,我们应用新颖的综合生物信息学分析证明,细胞膜部分的 NF-kappa-Beta-p65 (RELA) 和全细胞裂解液中的 Calpain-2 (CAPN2) 在 KD 中显著上调,并与包括细胞凋亡在内的相关关键信号通路的改变有关。流式细胞术和免疫组化显示,RELA 和 CAPN2 在 KD 中上调,进一步证实了我们的发现。此外,使用实时细胞分析和流式细胞术进行的功能评估表明,奥美拉唑和地塞米松都能通过提高细胞凋亡率来抑制 KD 成纤维细胞的生长。总之,据我们所知,亚细胞分馏和元蛋白基因组分析发现了两种与瘢痕疙瘩诊断和治疗相关的新型生物标志物,它们以前从未报道过。
{"title":"Subcellular Fractionation and Metaproteogenomic Identification and Validation of Key Differentially Expressed Molecular Targets for Keloid Disease.","authors":"Elvis B Kidzeru, Musalula Sinkala, Temwani Chalwa, Relebohile Matobole, Madeha Alkelani, Zeinab Ghasemishahrestani, Stanley K Mbandi, Jonathan Blackburn, David L Tabb, Henry Ademola Adeola, Nonhlanhla P Khumalo, Ardeshir Bayat","doi":"10.1016/j.jid.2024.07.010","DOIUrl":"10.1016/j.jid.2024.07.010","url":null,"abstract":"<p><p>Keloid disease (KD) is a common connective tissue disorder of unknown aetiopathogenesis with ill-defined treatment. Keloid scars present as exophytic fibroproliferative reticular lesions postcutaneous injury, and even though KD remains neoplastically benign, keloid lesions behave locally aggressive, invasive and expansive. To date, there is limited understanding and validation of biomarkers identified through combined proteomic and genomic evaluation of KD. Therefore, the aim in this study was to identify putative causative candidates in KD by performing a comprehensive proteomics analysis of subcellular fractions as well as the whole cell, coupled with transcriptomics data analysis of normal compared with KD fibroblasts. We then applied novel integrative bioinformatics analysis to demonstrate that NF-kB-p65 (RELA) from the cytosolic fraction and CAPN2 from the whole-cell lysate were statistically significantly upregulated in KD and associated with alterations in relevant key signaling pathways, including apoptosis. Our findings were further confirmed by showing upregulation of both RELA and CAPN2 in KD using flow cytometry and immunohistochemistry. Moreover, functional evaluation using real-time cell analysis and flow cytometry demonstrated that both omeprazole and dexamethasone inhibited the growth of KD fibroblasts by enhancing the rate of apoptosis. In conclusion, subcellular fractionation and metaproteogenomic analyses have identified, to our knowledge, 2 previously unreported biomarkers of significant relevance to keloid diagnostics and therapeutics.</p>","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multiplexed Mass Cytometry of Cutaneous Lupus Erythematosus and Dermatomyositis Skin: An In-depth, B-Cell-Directed Immunoprofile. 皮肤红斑狼疮和皮肌炎皮肤的多重质量细胞测定法:深入的 B 细胞定向免疫概况。
Pub Date : 2024-08-03 DOI: 10.1016/j.jid.2024.07.007
Mariko Ogawa-Momohara, Thomas Vazquez, Felix Chin, Meena Sharma, Joshua Dan, Grant Sprow, Victoria P Werth
{"title":"Multiplexed Mass Cytometry of Cutaneous Lupus Erythematosus and Dermatomyositis Skin: An In-depth, B-Cell-Directed Immunoprofile.","authors":"Mariko Ogawa-Momohara, Thomas Vazquez, Felix Chin, Meena Sharma, Joshua Dan, Grant Sprow, Victoria P Werth","doi":"10.1016/j.jid.2024.07.007","DOIUrl":"10.1016/j.jid.2024.07.007","url":null,"abstract":"","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mechanical Stretch Exacerbates Imiquimod-Induced Dermatitis Associated with Increased IL-1β and IL-6 Production. 机械拉伸会加剧咪喹莫特诱发的皮炎,并导致IL-1β和IL-6分泌增加
Pub Date : 2024-08-03 DOI: 10.1016/j.jid.2024.07.015
Chaw-Ning Lee, Yi-Kai Hong, Hui-Ching Cheng, Wan-Yu Chi, Wei-Chen Lin, Chao-Kai Hsu, Yu-Chen Lin, Shu-Yi Cheng, Ming-Jer Tang, Chao-Chun Yang
{"title":"Mechanical Stretch Exacerbates Imiquimod-Induced Dermatitis Associated with Increased IL-1β and IL-6 Production.","authors":"Chaw-Ning Lee, Yi-Kai Hong, Hui-Ching Cheng, Wan-Yu Chi, Wei-Chen Lin, Chao-Kai Hsu, Yu-Chen Lin, Shu-Yi Cheng, Ming-Jer Tang, Chao-Chun Yang","doi":"10.1016/j.jid.2024.07.015","DOIUrl":"10.1016/j.jid.2024.07.015","url":null,"abstract":"","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141895126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Endolysins Target Bad Neighbors in the Wound Microbial Community. 内切酶瞄准伤口微生物群落中的坏邻居
Pub Date : 2024-07-30 DOI: 10.1016/j.jid.2024.06.1277
David O Croitoru, Vincent Piguet
{"title":"Endolysins Target Bad Neighbors in the Wound Microbial Community.","authors":"David O Croitoru, Vincent Piguet","doi":"10.1016/j.jid.2024.06.1277","DOIUrl":"https://doi.org/10.1016/j.jid.2024.06.1277","url":null,"abstract":"","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pub Date : 2024-07-30 DOI: 10.1016/j.jid.2024.04.002
{"title":"","authors":"","doi":"10.1016/j.jid.2024.04.002","DOIUrl":"https://doi.org/10.1016/j.jid.2024.04.002","url":null,"abstract":"","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
IRAK4 Is Overexpressed in Hidradenitis Suppurativa Skin and Correlates with Inflammatory Biomarkers. 白细胞介素 1 受体相关激酶 4 在扁平苔藓皮肤中过度表达并与炎症生物标志物相关
Pub Date : 2024-07-29 DOI: 10.1016/j.jid.2024.04.035
Alice McDonald, Rahul Karnik, Veronica Campbell, Jeff Davis, Sara Chavoshi, Anthony Slavin, Kirti Sharma, Jared Gollob, Afsaneh Alavi

Hidradenitis suppurativa (HS) is a chronic inflammatory disease manifesting as painful dermal nodules, abscesses, and tunnels. Activation of the IL-1R/toll-like receptor pathway is strongly implicated in the pathogenesis of HS; thus, the role of a key signaling node, IRAK4, was investigated in a noninterventional study (NCT04440410) that enrolled 30 patients with HS. IRAK4 expression was evaluated in blood and lesional, perilesional, and nonlesional skin biopsies. PBMCs expressed IRAK4, with significantly higher levels in monocytes (P ≤ .0001). Ex vivo treatment of PBMCs with KT-474, a targeted degrader of IRAK4, robustly decreased IRAK4 in all immune cell types from healthy volunteers and patients with HS. Ex vivo treatment of toll-like receptor-stimulated healthy donor monocytes with KT-474 decreased IRAK4 protein levels and inhibited inflammatory cytokine production. In HS skin samples, IRAK4 protein levels were significantly higher in lesional than in nonlesional tissue (P ≤ .0001), and IRAK4-positive immune infiltrate increased with greater disease severity. Multiple inflammatory mediators were upregulated in HS lesional skin, correlating with IRAK4 overexpression. These data confirm the significance of the IL-1R/toll-like receptor pathway in the pathogenesis of HS and provide support for ongoing clinical studies evaluating KT-474 in the treatment of HS.

化脓性扁平湿疹(Hidradenitis suppurativa,HS)是一种慢性炎症性疾病,表现为疼痛性真皮结节、脓肿和隧道。IL-1R/toll样受体(TLR)通路的激活与化脓性扁平湿疹的发病机制密切相关;因此,在一项纳入了30名化脓性扁平湿疹患者的非介入性研究(NCT04440410)中,研究人员对一个关键信号节点IL-1R相关激酶4(IRAK4)的作用进行了调查。该研究评估了血液、皮损、皮损周围和非皮损皮肤活检组织中 IRAK4 的表达。外周血单核细胞(PBMCs)表达 IRAK4,其中单核细胞的表达水平明显更高(P ≤ 0.0001)。用 IRAK4 的靶向降解剂 KT-474 对 PBMCs 进行体外处理,可显著降低健康志愿者和 HS 患者所有免疫细胞类型中的 IRAK4 含量。用 KT-474 对 TLR 刺激的健康供体单核细胞进行体外处理,可降低 IRAK4 蛋白水平并抑制炎性细胞因子的产生。在 HS 皮肤样本中,病变组织的 IRAK4 蛋白水平明显高于非病变组织(P ≤ 0.0001),IRAK4 阳性免疫浸润随着疾病严重程度的增加而增加。HS 病变皮肤中多种炎症介质上调,与 IRAK4 过度表达相关。这些数据证实了IL-1R/TLR通路在HS发病机制中的重要性,并为正在进行的评估KT-474治疗HS的临床研究提供了支持。
{"title":"IRAK4 Is Overexpressed in Hidradenitis Suppurativa Skin and Correlates with Inflammatory Biomarkers.","authors":"Alice McDonald, Rahul Karnik, Veronica Campbell, Jeff Davis, Sara Chavoshi, Anthony Slavin, Kirti Sharma, Jared Gollob, Afsaneh Alavi","doi":"10.1016/j.jid.2024.04.035","DOIUrl":"10.1016/j.jid.2024.04.035","url":null,"abstract":"<p><p>Hidradenitis suppurativa (HS) is a chronic inflammatory disease manifesting as painful dermal nodules, abscesses, and tunnels. Activation of the IL-1R/toll-like receptor pathway is strongly implicated in the pathogenesis of HS; thus, the role of a key signaling node, IRAK4, was investigated in a noninterventional study (NCT04440410) that enrolled 30 patients with HS. IRAK4 expression was evaluated in blood and lesional, perilesional, and nonlesional skin biopsies. PBMCs expressed IRAK4, with significantly higher levels in monocytes (P ≤ .0001). Ex vivo treatment of PBMCs with KT-474, a targeted degrader of IRAK4, robustly decreased IRAK4 in all immune cell types from healthy volunteers and patients with HS. Ex vivo treatment of toll-like receptor-stimulated healthy donor monocytes with KT-474 decreased IRAK4 protein levels and inhibited inflammatory cytokine production. In HS skin samples, IRAK4 protein levels were significantly higher in lesional than in nonlesional tissue (P ≤ .0001), and IRAK4-positive immune infiltrate increased with greater disease severity. Multiple inflammatory mediators were upregulated in HS lesional skin, correlating with IRAK4 overexpression. These data confirm the significance of the IL-1R/toll-like receptor pathway in the pathogenesis of HS and provide support for ongoing clinical studies evaluating KT-474 in the treatment of HS.</p>","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Senescent Dermal Fibroblasts Decrease Stemness in Basal Keratinocytes in a Bioengineered Model of Human Full-Thickness Skin. 在生物工程人体全厚皮肤模型中,衰老的真皮成纤维细胞会降低基底角质细胞的干性。
Pub Date : 2024-07-22 DOI: 10.1016/j.jid.2024.07.004
Evon Low, Lucy A Smith, Satomi Miwa, Edward Fielder, Stefan Przyborski, Thomas von Zglinicki
{"title":"Senescent Dermal Fibroblasts Decrease Stemness in Basal Keratinocytes in a Bioengineered Model of Human Full-Thickness Skin.","authors":"Evon Low, Lucy A Smith, Satomi Miwa, Edward Fielder, Stefan Przyborski, Thomas von Zglinicki","doi":"10.1016/j.jid.2024.07.004","DOIUrl":"10.1016/j.jid.2024.07.004","url":null,"abstract":"","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
The Journal of investigative dermatology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1