Protein & CellPub Date : 2025-03-22DOI: 10.1093/procel/pwaf024
Fathima Athar, Francesco Morandini, Iqra Fatima, Isabella Silvestri, Seijoong Brian Kim, Minseon Lee, Xiaoyan Liao, Andrei Sharov, Vladimir Botchkarev, Andrei Seluanov, Vera Gorbunova
{"title":"African spiny mice show resistance to DMBA/TPA-induced squamous carcinogenesis with distinct benign tumor profile.","authors":"Fathima Athar, Francesco Morandini, Iqra Fatima, Isabella Silvestri, Seijoong Brian Kim, Minseon Lee, Xiaoyan Liao, Andrei Sharov, Vladimir Botchkarev, Andrei Seluanov, Vera Gorbunova","doi":"10.1093/procel/pwaf024","DOIUrl":"10.1093/procel/pwaf024","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"High-throughput single-microbe RNA sequencing reveals adaptive state heterogeneity and host-phage activity associations in human gut microbiome.","authors":"Yifei Shen, Qinghong Qian, Liguo Ding, Wenxin Qu, Tianyu Zhang, Mengdi Song, Yingjuan Huang, Mengting Wang, Ziye Xu, Jiaye Chen, Ling Dong, Hongyu Chen, Enhui Shen, Shufa Zheng, Yu Chen, Jiong Liu, Longjiang Fan, Yongcheng Wang","doi":"10.1093/procel/pwae027","DOIUrl":"10.1093/procel/pwae027","url":null,"abstract":"<p><p>Microbial communities such as those residing in the human gut are highly diverse and complex, and many with important implications for health and diseases. The effects and functions of these microbial communities are determined not only by their species compositions and diversities but also by the dynamic intra- and inter-cellular states at the transcriptional level. Powerful and scalable technologies capable of acquiring single-microbe-resolution RNA sequencing information in order to achieve a comprehensive understanding of complex microbial communities together with their hosts are therefore utterly needed. Here we report the development and utilization of a droplet-based smRNA-seq (single-microbe RNA sequencing) method capable of identifying large species varieties in human samples, which we name smRandom-seq2. Together with a triple-module computational pipeline designed for the bacteria and bacteriophage sequencing data by smRandom-seq2 in four human gut samples, we established a single-cell level bacterial transcriptional landscape of human gut microbiome, which included 29,742 single microbes and 329 unique species. Distinct adaptive response states among species in Prevotella and Roseburia genera and intrinsic adaptive strategy heterogeneity in Phascolarctobacterium succinatutens were uncovered. Additionally, we identified hundreds of novel host-phage transcriptional activity associations in the human gut microbiome. Our results indicated that smRandom-seq2 is a high-throughput and high-resolution smRNA-seq technique that is highly adaptable to complex microbial communities in real-world situations and promises new perspectives in the understanding of human microbiomes.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"211-226"},"PeriodicalIF":13.6,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11891138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141082073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Protein & CellPub Date : 2025-03-08DOI: 10.1093/procel/pwae041
Chao Yang, Longfeng Yao, Dan Chen, Changling Chen, Wenbo Li, Hua Tong, Zihang Cheng, Yanling Yan, Long Lin, Jing Zhang, Anbing Shi
{"title":"Endosomal catabolism of phosphatidylinositol 4,5-bisphosphate is fundamental in building resilience against pathogens.","authors":"Chao Yang, Longfeng Yao, Dan Chen, Changling Chen, Wenbo Li, Hua Tong, Zihang Cheng, Yanling Yan, Long Lin, Jing Zhang, Anbing Shi","doi":"10.1093/procel/pwae041","DOIUrl":"10.1093/procel/pwae041","url":null,"abstract":"<p><p>Endosomes are characterized by the presence of various phosphoinositides that are essential for defining the membrane properties. However, the interplay between endosomal phosphoinositides metabolism and innate immunity is yet to be fully understood. Here, our findings highlight the evolutionary continuity of RAB-10/Rab10's involvement in regulating innate immunity. Upon infection of Caenorhabditis elegans with Pseudomonas aeruginosa, an increase in RAB-10 activity was observed in the intestine. Conversely, when RAB-10 was absent, the intestinal diacylglycerols (DAGs) decreased, and the animal's response to the pathogen was impaired. Further research revealed that UNC-16/JIP3 acts as an RAB-10 effector, facilitating the recruitment of phospholipase EGL-8 to endosomes. This leads to a decrease in endosomal phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and an elevation of DAGs, as well as the activation of the PMK-1/p38 MAPK innate immune pathway. It is noteworthy that the dimerization of UNC-16 is a prerequisite for its interaction with RAB-10(GTP) and the recruitment of EGL-8. Moreover, we ascertained that the rise in RAB-10 activity, due to infection, was attributed to the augmented expression of LET-413/Erbin, and the nuclear receptor NHR-25/NR5A1/2 was determined to be indispensable for this increase. Hence, this study illuminates the significance of endosomal PI(4,5)P2 catabolism in boosting innate immunity and outlines an NHR-25-mediated mechanism for pathogen detection in intestinal epithelia.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"161-187"},"PeriodicalIF":13.6,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11891140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"IL-24 promotes atopic dermatitis-like inflammation through driving MRSA-induced allergic responses.","authors":"Xinmin Qian, Meiyi Tong, Tianqing Zhang, Qingqing Li, Meng Hua, Nan Zhou, Wenwen Zeng","doi":"10.1093/procel/pwae030","DOIUrl":"10.1093/procel/pwae030","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching. The colonization of Staphylococcus aureus (S. aureus) is correlated with the severity of the disease, but its role in AD development remains elusive. Using single-cell RNA sequencing, we uncovered that keratinocytes activate a distinct immune response characterized by induction of Il24 when exposed to methicillin-resistant S. aureus (MRSA). Further experiments using animal models showed that the administration of recombinant IL-24 protein worsened AD-like pathology. Genetic ablation of Il24 or the receptor Il20rb in keratinocytes alleviated allergic inflammation and atopic march. Mechanistically, IL-24 acted through its heterodimeric receptors on keratinocytes and augmented the production of IL-33, which in turn aggravated type 2 immunity and AD-like skin conditions. Overall, these findings establish IL-24 as a critical factor for onset and progression of AD and a compelling therapeutic target.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"188-210"},"PeriodicalIF":13.6,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neutrophil extracellular traps license macrophage production of chemokines to facilitate CD8+ T cell infiltration in obstruction-induced renal fibrosis.","authors":"Hongshuai Jia, Guang Yue, Pin Li, Renjun Peng, Ruyue Jin, Yuhan Chen, Hualin Cao, Kangning Yang, Xiaowei Zhang, Xiaoyu Yi, Yangyang Wu, Xiangling Deng, Xiaoye Chen, Lifei Ma, Yang Zhao, Xiaoguang Zhou, Tian Tao, Xiaoli Shen, Xu Zhang, Yuandong Tao, Huixia Zhou","doi":"10.1093/procel/pwaf020","DOIUrl":"https://doi.org/10.1093/procel/pwaf020","url":null,"abstract":"<p><p>Renal fibrosis is a common mechanism leading to kidney failure in chronic kidney diseases (CKDs), including obstructive nephropathy (ON). Dysregulated inflammation is central to the development of renal fibrosis, but how local immune cells within the tissue microenvironment integrate and coordinate to drive this condition remains largely unknown. Herein, we documented that neutrophils were abundantly recruited and expelled neutrophil extracellular traps (NETs) in human and mouse fibrotic kidneys. Importantly, circulating levels of NET components displayed a significant correlation with worsened kidney function in ON patients. In the unilateral ureteral obstruction (UUO) mouse model, blocking NETs by protein-arginine deiminase type 4 (PAD4) deletion or DNase treatment significantly impaired NET formation and inhibited renal fibrosis and inflammation, whereas NET adoptive transfer exacerbated the fibrotic process. Moreover, NET-mediated renal fibrosis was associated with enhanced infiltration of cytotoxic CD8+ T cells, which produced granzyme B (GZMB) to drive tubular cell epithelial-mesenchymal transition (EMT) and fibroblast activation. Accordingly, pharmacological inhibition of GZMB resulted in blunted kidney inflammation and fibrosis. Furthermore, NETs profoundly potentiated the production of T-cell chemokines CXCL9/10/11 in macrophages, but not in tubular cells or fibroblasts, thus driving T-cell infiltration and fueling inflammatory cascades in the kidneys. Mechanistically, the NET-macrophage interaction was partially mediated by the TLR2/4 signaling. Thus, our work reveals a previously unexplored role of the collaboration between NETs and macrophages in supporting CD8+ T cell infiltration, which orchestrates kidney inflammation and fibrosis.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Protein & CellPub Date : 2025-02-20DOI: 10.1093/procel/pwaf009
{"title":"Correction to: CRISPR/Cas9-mediated gene knockout reveals a guardian role of NF-κB/RelA in maintaining the homeostasis of human vascular cells.","authors":"","doi":"10.1093/procel/pwaf009","DOIUrl":"https://doi.org/10.1093/procel/pwaf009","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}