The Journal of investigative dermatology最新文献_第10页

Fibroblast-Mediated Macrophage Recruitment Supports Acute Wound Healing. 成纤维细胞介导的巨噬细胞招募支持急性伤口愈合。

The Journal of investigative dermatology Pub Date : 2024-11-22 DOI: 10.1016/j.jid.2024.10.609

Veronica M Amuso, MaryEllen R Haas, Paula O Cooper, Ranojoy Chatterjee, Sana Hafiz, Shatha Salameh, Chiraag Gohel, Miguel F Mazumder, Violet Josephson, Sarah S Kleb, Khatereh Khorsandi, Anelia Horvath, Ali Rahnavard, Brett A Shook

{"title":"Fibroblast-Mediated Macrophage Recruitment Supports Acute Wound Healing.","authors":"Veronica M Amuso, MaryEllen R Haas, Paula O Cooper, Ranojoy Chatterjee, Sana Hafiz, Shatha Salameh, Chiraag Gohel, Miguel F Mazumder, Violet Josephson, Sarah S Kleb, Khatereh Khorsandi, Anelia Horvath, Ali Rahnavard, Brett A Shook","doi":"10.1016/j.jid.2024.10.609","DOIUrl":"10.1016/j.jid.2024.10.609","url":null,"abstract":"Epithelial and immune cells have long been appreciated for their contribution to the early immune response after injury; however, much less is known about the role of mesenchymal cells. Using single-nuclei RNA sequencing, we defined changes in gene expression associated with inflammation 1 day after wounding in mouse skin. Compared with those in keratinocytes and myeloid cells, we detected enriched expression of proinflammatory genes in fibroblasts associated with deeper layers of the skin. In particular, SCA1+ fibroblasts were enriched for numerous chemokines, including CCL2, CCL7, and IL-33, compared with SCA1- fibroblasts. Genetic deletion of Ccl2 in fibroblasts resulted in fewer wound-bed macrophages and monocytes during injury-induced inflammation, with reduced revascularization and re-epithelialization during the proliferation phase of healing. These findings highlight the important contribution of fibroblast-derived factors to injury-induced inflammation and the impact of immune cell dysregulation on subsequent tissue repair.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712336","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

Skin-Resident γδ T Cells Mediate Potent and Selective Antitumor Cytotoxicity through Directed Chemotactic Migration and Mobilization of Cytotoxic Granules. 皮肤驻留的γδ T 细胞通过定向趋化迁移和细胞毒性颗粒的动员，介导强效和选择性的抗肿瘤细胞毒性。

The Journal of investigative dermatology Pub Date : 2024-11-20 DOI: 10.1016/j.jid.2024.10.607

Jiacai Yang, Zhihui Liu, Xiaohong Hu, Xiaorong Zhang, Yong Huang, Yunxia Chen, Cheng Chen, Ruoyu Shang, Yuanyang Tang, Wengang Hu, Jue Wang, Han-Ming Shen, Jun Hu, Weifeng He

{"title":"Skin-Resident γδ T Cells Mediate Potent and Selective Antitumor Cytotoxicity through Directed Chemotactic Migration and Mobilization of Cytotoxic Granules.","authors":"Jiacai Yang, Zhihui Liu, Xiaohong Hu, Xiaorong Zhang, Yong Huang, Yunxia Chen, Cheng Chen, Ruoyu Shang, Yuanyang Tang, Wengang Hu, Jue Wang, Han-Ming Shen, Jun Hu, Weifeng He","doi":"10.1016/j.jid.2024.10.607","DOIUrl":"10.1016/j.jid.2024.10.607","url":null,"abstract":"Dendritic epidermal T cells (DETCs) are a unique subset of γδ T cells that reside predominantly in mouse epidermis; yet, their antitumor functions remain enigmatic. In this study, we report that DETCs mediate potent and exquisitely selective cytotoxicity against diverse tumor types while sparing healthy cells. In vitro, DETCs induced apoptosis in melanoma, hepatoma, colon carcinoma, and lymphoma lines in a dose- and time-dependent manner that required direct cell-cell contact. In vivo, adoptive DETC transfer significantly suppressed melanoma growth and metastasis while prolonging survival. Mechanistically, DETCs upregulated perforin/granzyme B expression upon tumor recognition, and inhibition of this pathway ablated cytotoxicity. DETCs selectively homed to and formed intimate contacts with tumor cells in vivo through directed chemotaxis and aggregation. Tumor engagement triggered proinflammatory DETC activation while dampening immunosuppressive factors in the microenvironment. Notably, mTOR signaling coupled tumor recognition to DETC trafficking, cytotoxicity, and inflammatory programs because rapamycin treatment impaired effector functions and therapeutic efficacy. Collectively, these findings establish DETCs as multidimensional antitumor effectors and provide insights for harnessing their unique biology for cancer immunotherapy.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690200","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

Role of ADAM10/17-Mediated Cleavage of LAG3 in the Impairment of Immunosuppression in Psoriasis. ADAM10/17 介导的 LAG3 分裂在银屑病免疫抑制损伤中的作用

The Journal of investigative dermatology Pub Date : 2024-11-20 DOI: 10.1016/j.jid.2024.10.606

Zengyang Yu, Xinyi Tang, Zeyu Chen, Yifan Hu, Shuqin Zhang, Chunyuan Guo, Jun Gu, Yuling Shi, Yu Gong

{"title":"Role of ADAM10/17-Mediated Cleavage of LAG3 in the Impairment of Immunosuppression in Psoriasis.","authors":"Zengyang Yu, Xinyi Tang, Zeyu Chen, Yifan Hu, Shuqin Zhang, Chunyuan Guo, Jun Gu, Yuling Shi, Yu Gong","doi":"10.1016/j.jid.2024.10.606","DOIUrl":"10.1016/j.jid.2024.10.606","url":null,"abstract":"Despite extensive research on immune activation regulatory mechanisms, studies on immune suppression in psoriasis are limited. LAG3, a newly identified immune checkpoint, plays a crucial role in modulating immune responses and maintaining T-regulatory cell function. However, its involvement in psoriasis is unclear. We show that psoriasis is associated with reduced LAG3 expression in CD4 T cells and T-regulatory cells. Further analysis revealed that the decline in LAG3 levels was linked to ADAM10/17-mediated proteolytic cleavage, which was upregulated in psoriasis. Clinical utilization of the IL-17A antagonist secukinumab, along with the in vivo and in vitro IL-17A-induced models, supported the potential of IL-17A to induce ADAM10/17 expression and trigger LAG3 cleavage. Through the Jurkat cell model, IL-17A was found to regulate ADAM10/17 expression by activating FOXM1. In addition, treatment with the ADAM10/17 inhibitor GW280264X showed ameliorative effects on psoriasis-like mouse models and lipopolysaccharide-induced inflammation. Collectively, the findings of this study uncover the immune regulatory role of the ADAM10/17-LAG3 axis in psoriasis and highlight the therapeutic potential of targeting ADAM10/17 for psoriasis treatment.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690199","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

Inhibition of Pyruvate Oxidation Diminishes Melanoma Progression. 抑制丙酮酸氧化可减少黑色素瘤的发展。

The Journal of investigative dermatology Pub Date : 2024-11-19 DOI: 10.1016/j.jid.2024.10.605

Berfin Seyran, Itzel Avila, Carlos Galvan, Genesis Robles, Conor Murphy, Heather R Christofk, William E Lowry

引用次数: 0

Blood-Borne Bone Marrow-Derived Epithelial Cells Searching for a Niche: The Epithelial Transit Hypothesis. 血源性骨髓上皮细胞寻找生态位：上皮转运假说。

The Journal of investigative dermatology Pub Date : 2024-11-19 DOI: 10.1016/j.jid.2024.10.603

Stephanie M Holtorf, Rebecca J Morris

引用次数: 0

Enhancer of TRPS1 rs12549956 Influences Hair Thickness in Chinese Populations. TRPS1 rs12549956 的增强子对中国人群头发厚度的影响。

The Journal of investigative dermatology Pub Date : 2024-11-14 DOI: 10.1016/j.jid.2024.10.601

Qili Qian, Sijie Wu, Junyu Luo, Yaqun Guan, Yajun Yang, Li Jin, Wenxin Zheng, Sijia Wang

引用次数: 0

The Clinical and Molecular Response of Pyoderma Gangrenosum to IL-23 Blockade: Result from a Proof-of-Concept Open-Label Clinical Trial. 脓皮病对白细胞介素 23 阻断剂的临床和分子反应：概念验证开放标签临床试验的结果。

The Journal of investigative dermatology Pub Date : 2024-11-14 DOI: 10.1016/j.jid.2024.10.602

Akshay Flora, James Pham, Jane A Woods, Michael Radzeika, Hugh Dickson, Mathew Malone, John W Frew

{"title":"The Clinical and Molecular Response of Pyoderma Gangrenosum to IL-23 Blockade: Result from a Proof-of-Concept Open-Label Clinical Trial.","authors":"Akshay Flora, James Pham, Jane A Woods, Michael Radzeika, Hugh Dickson, Mathew Malone, John W Frew","doi":"10.1016/j.jid.2024.10.602","DOIUrl":"10.1016/j.jid.2024.10.602","url":null,"abstract":"Pyoderma gangrenosum is a severe ulcerative disease with a great need for novel therapies. A major barrier to the development of novel therapies is a lack of understanding of disease pathogenesis. We present the results of a proof-of-concept open-label clinical trial of IL-23p19 antagonism with tildrakizumab in pyoderma gangrenosum. Gene expression analysis identified proinflammatory genes associated with IFN responses and dendritic cell activity, including IFI27, XBP1, SAA1 LGALS3, and signal transducer and activator of transcription 3 significantly downregulated in lesional tissue after 12 weeks of therapy. Immunohistochemistry confirmed reduction in IL-17A- and IL-17F-positive cells as well as reduction in TNF-a-, C5a-, and IL-1B-positive cells in week 12 samples compared with those at baseline. Significant reduction in serum inflammation was observed through serum proteomics, with IL-8, IL-6, and CASP-8 levels reduced comparable with those in healthy controls at week 12. Clinical outcomes demonstrated significant reduction in ulcer size, pain, itch, and QOL outcomes in line with the molecular findings. Differential expression of key inflammatory cytokines such as IL-8, CXCL5, PD-L1, SPP1, and matrix metalloproteinase 1 was observed in tissue and serum when stratified by clinical responders and nonresponders. These data provide insights into the clinical relevance of alterations in molecular markers in pyoderma gangrenosum and the potential for the identification of clinically relevant biomarkers of disease activity.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640535","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

Apocrine Gland Damage and the Release of Specific Keratins in Early Stage Indicate the Crucial Involvement of Apocrine Glands in Hidradenitis Suppurativa. 分泌腺损伤和早期特异性角蛋白的释放表明，分泌腺在化脓性扁桃体炎中起着至关重要的作用。

The Journal of investigative dermatology Pub Date : 2024-11-14 DOI: 10.1016/j.jid.2024.09.021

Jiaqi Li, Sitong Li, Qiujing Zhang, Mengchen Liang, Xiang Chen, Yibo Feng, Zhanyan Pan, Tingting Hu, Qiong Wu, Guangjie Chen, Christos C Zouboulis, Xiaohui Mo, Qiang Ju

{"title":"Apocrine Gland Damage and the Release of Specific Keratins in Early Stage Indicate the Crucial Involvement of Apocrine Glands in Hidradenitis Suppurativa.","authors":"Jiaqi Li, Sitong Li, Qiujing Zhang, Mengchen Liang, Xiang Chen, Yibo Feng, Zhanyan Pan, Tingting Hu, Qiong Wu, Guangjie Chen, Christos C Zouboulis, Xiaohui Mo, Qiang Ju","doi":"10.1016/j.jid.2024.09.021","DOIUrl":"10.1016/j.jid.2024.09.021","url":null,"abstract":"The apocrine glands (AGs) are not considered to be primarily involved in hidradenitis suppurativa (HS). This study investigated the potential role of AGs in HS pathogenesis using immunohistochemistry and single-cell sequencing of nonlesional skin and early lesional skin (LS) from patients with HS (n = 12) and healthy controls (n = 8). AG cell destruction was more frequent, and AG size was significantly reduced in the nonlesional skin and LS. Barrier-related genes (eg, CLDN1 and CDH1) were downregulated in the AGs of the nonlesional skin and LS. Damaged AGs in the LS primarily recruited and activated neutrophils through the CXCL-CXCR and SAA1-FPR2 pathways. Elevated levels of specific keratins (keratin 18 and keratin 19) released from damaged AGs were observed on the skin surface of patients and were associated with disease severity. Keratin 19 was also detected in the dermis of the nonlesional skin and LS and was surrounded by neutrophils and macrophages. Moreover, serum keratin 19 levels in patients (N = 20) were significantly negatively correlated with the age at HS onset. Collectively, our findings provide previously unreported evidence that the AGs are damaged and release specific keratins in early HS lesions, indicating a crucial role of the AGs in HS pathogenesis.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640532","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

FOXO3A Plays a Role in Wound Healing by Regulating Fibroblast Mitochondrial Dynamics. FoxO3a 通过调节成纤维细胞线粒体动力学在伤口愈合中发挥作用

The Journal of investigative dermatology Pub Date : 2024-11-14 DOI: 10.1016/j.jid.2024.10.600

Mariko Moriyama, Ryoichi Mori, Takao Hayakawa, Hiroyuki Moriyama

{"title":"FOXO3A Plays a Role in Wound Healing by Regulating Fibroblast Mitochondrial Dynamics.","authors":"Mariko Moriyama, Ryoichi Mori, Takao Hayakawa, Hiroyuki Moriyama","doi":"10.1016/j.jid.2024.10.600","DOIUrl":"10.1016/j.jid.2024.10.600","url":null,"abstract":"The skin plays a protective role against harmful environmental stress such as UV rays. Therefore, the skin is constantly exposed to potential injuries, and wound healing is a vital process for the survival of all higher organisms. Wound healing is dependent on aging and metabolic status at a whole-body level. Because the FOXO family plays a role in aging and metabolism, we investigated the molecular functions of FOXO3A in skin wound healing using FoxO3a-/- mice. We observed that FoxO3a-/- mice showed accelerated skin wound healing. During wound healing, more fibroblasts accumulated at the wound edges and migrated into the wound bed in FoxO3a-/- mice. Moreover, cell migration of dermal fibroblasts isolated from FoxO3a-/- mice was significantly induced. During the in vitro cell migration, we observed accelerated mitochondrial fragmentation and decreased oxygen consumption in the mitochondria of FoxO3a-/- fibroblasts. These changes were caused by the upregulation of mitochondrial Rho GTPase 1, which is an essential mediator of microtubule-based mitochondrial motility. Mitochondrial Rho GTPase 1 inhibition significantly attenuated cell migration, mitochondrial fragmentation, and mitochondrial recruitment to the leading edge of the cells. These data indicate that FOXO3A plays a crucial role in wound healing by regulating mitochondrial dynamics.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640534","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

Increased Mortality in Patients with Diffuse Systemic Sclerosis with High Circulating IFNα Levels. 循环 IFNα 水平较高的弥漫性系统性硬化症患者死亡率增加。

The Journal of investigative dermatology Pub Date : 2024-11-13 DOI: 10.1016/j.jid.2024.09.020

François Maillet, Carine Schmidt, Vincent Bondet, Alexandre Bense, Darragh Duffy, Luc Mouthon, Mathieu Paul Rodero, Benjamin Chaigne

引用次数: 0