Pub Date : 2026-01-01DOI: 10.1016/j.hlife.2025.09.006
Jiaqi Li , Letong Yang , Xiwen Qin , Min Zhao , Shuo Wang
The local immune system of the lungs is essential for the defense against pathogens, and respiratory bacterial infections remain a major cause of mortality in patients with lower respiratory tract diseases. However, the precise mechanisms underlying immune–pathogen interactions and the modulatory roles of commensal bacteria remain incompletely understood. This review discusses the mechanisms of immune recognition and inflammatory responses during bacterial respiratory bacterial infections, highlighting the importance of pattern recognition receptors, including toll-like receptors, nucleotide oligomerization domain-like receptors, and C-type lectin receptors in detecting pathogens and triggering immune signaling pathways. We also explore how commensal bacteria influence the respiratory immune microenvironment and discuss the complex interplay among pathogenic bacteria, commensals, and the host pulmonary immune system. This analysis provides a theoretical foundation for the development of targeted therapeutics against bacterial respiratory infections.
{"title":"Interplay between bacteria and pulmonary immune system in respiratory infections","authors":"Jiaqi Li , Letong Yang , Xiwen Qin , Min Zhao , Shuo Wang","doi":"10.1016/j.hlife.2025.09.006","DOIUrl":"10.1016/j.hlife.2025.09.006","url":null,"abstract":"<div><div>The local immune system of the lungs is essential for the defense against pathogens, and respiratory bacterial infections remain a major cause of mortality in patients with lower respiratory tract diseases. However, the precise mechanisms underlying immune–pathogen interactions and the modulatory roles of commensal bacteria remain incompletely understood. This review discusses the mechanisms of immune recognition and inflammatory responses during bacterial respiratory bacterial infections, highlighting the importance of pattern recognition receptors, including toll-like receptors, nucleotide oligomerization domain-like receptors, and C-type lectin receptors in detecting pathogens and triggering immune signaling pathways. We also explore how commensal bacteria influence the respiratory immune microenvironment and discuss the complex interplay among pathogenic bacteria, commensals, and the host pulmonary immune system. This analysis provides a theoretical foundation for the development of targeted therapeutics against bacterial respiratory infections.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 1","pages":"Pages 3-15"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145872151","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}
Pub Date : 2026-01-01DOI: 10.1016/j.hlife.2025.10.006
Yinchun Chen , Ruiqing Zhou , Limei Zhong , Haimei Deng , Jun Yu , Huijuan Wang , Xiaotao Jiang , Wenjian Mo , Shunqing Wang , Yufeng Liu
Accurate prediction and monitoring of acute graft-versus-host disease (aGVHD) remain challenging in allogeneic hematopoietic stem cell transplantation (allo-HSCT) as current diagnostic approaches rely on symptomatic presentation. Therefore, this study sought to identify predictive biomarkers and therapeutic targets for aGVHD through longitudinal immune monitoring and mechanistic investigations. In this study, peripheral blood samples were collected weekly for 100 days from a group of 115 allo-HSCT recipients. CD38+HLA-DR+CD8+ T (activated CD8+ T) cells were analyzed using the t-distributed stochastic neighbor embedding (t-SNE) algorithm for high-dimensional data visualization and population identification. Clinical data integration was used to assess biomarker utility. Mechanistic studies included interleukin-15 (IL-15) stimulation, signaling pathway inhibition, cytotoxicity assays, and xenogeneic GVHD modeling with anti-CD38 (daratumumab) intervention. Our results revealed that sustained elevation of activated CD8+ T cells (> 36.6%) within the first month post-transplantation predicted aGVHD onset with high accuracy (AUC = 0.84, P < 0.001). Cell frequency dynamically correlated with treatment outcome, decreasing substantially in responders. Mechanistically, IL-15 drove T-cell receptor (TCR)-independent cytotoxicity via PI3K/mTOR activation, mediated by natural killer group 2D (NKG2D) and major histocompatibility complex class I chain related proteins A (MIC-α) interactions, validated by reduced K562 cell lysis following antibody blockade. In an 8–10-week-old NSG mouse model for xenogeneic transplantation, treatment with daratumumab (5 mg/kg) effectively lowered histopathological damage and increased survival. In conclusion, activated CD8+ T cells can serve as dual-purpose biomarkers for early aGVHD prediction and treatment monitoring. Their IL-15-driven cytotoxicity represents a targetable pathway, with daratumumab demonstrating therapeutic efficacy.
{"title":"Longitudinal analysis identifies bystander-activated innate cytotoxic CD8+ T cells as predictors and therapeutic biomarkers for acute graft-versus-host disease","authors":"Yinchun Chen , Ruiqing Zhou , Limei Zhong , Haimei Deng , Jun Yu , Huijuan Wang , Xiaotao Jiang , Wenjian Mo , Shunqing Wang , Yufeng Liu","doi":"10.1016/j.hlife.2025.10.006","DOIUrl":"10.1016/j.hlife.2025.10.006","url":null,"abstract":"<div><div>Accurate prediction and monitoring of acute graft-versus-host disease (aGVHD) remain challenging in allogeneic hematopoietic stem cell transplantation (allo-HSCT) as current diagnostic approaches rely on symptomatic presentation. Therefore, this study sought to identify predictive biomarkers and therapeutic targets for aGVHD through longitudinal immune monitoring and mechanistic investigations. In this study, peripheral blood samples were collected weekly for 100 days from a group of 115 allo-HSCT recipients. CD38<sup>+</sup>HLA-DR<sup>+</sup>CD8<sup>+</sup> T (activated CD8<sup>+</sup> T) cells were analyzed using the t-distributed stochastic neighbor embedding (t-SNE) algorithm for high-dimensional data visualization and population identification. Clinical data integration was used to assess biomarker utility. Mechanistic studies included interleukin-15 (IL-15) stimulation, signaling pathway inhibition, cytotoxicity assays, and xenogeneic GVHD modeling with anti-CD38 (daratumumab) intervention. Our results revealed that sustained elevation of activated CD8<sup>+</sup> T cells (> 36.6%) within the first month post-transplantation predicted aGVHD onset with high accuracy (AUC = 0.84, <em>P</em> < 0.001). Cell frequency dynamically correlated with treatment outcome, decreasing substantially in responders. Mechanistically, IL-15 drove T-cell receptor (TCR)-independent cytotoxicity <em>via</em> PI3K/mTOR activation, mediated by natural killer group 2D (NKG2D) and major histocompatibility complex class I chain related proteins A (MIC-α) interactions, validated by reduced K562 cell lysis following antibody blockade. In an 8–10-week-old NSG mouse model for xenogeneic transplantation, treatment with daratumumab (5 mg/kg) effectively lowered histopathological damage and increased survival. In conclusion, activated CD8<sup>+</sup> T cells can serve as dual-purpose biomarkers for early aGVHD prediction and treatment monitoring. Their IL-15-driven cytotoxicity represents a targetable pathway, with daratumumab demonstrating therapeutic efficacy.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 1","pages":"Pages 20-40"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145872153","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}
Pub Date : 2026-01-01DOI: 10.1016/j.hlife.2025.09.003
Zihao Deng , Jiazhen Luo , Yufu Zhang , Chen Li , Shixin Deng , Jiazhi He , Zihao He , Wenqi Wu , Renjie Jiao , Jiyong Liu
Trained immunity is essential for innate immune cells to retain a memory of previously encountered pathogens, strengthening the hosts’ response against these pathogens. However, the mechanisms governing trained immunity have not been well elucidated. In this study, flies of different genotypes were trained with heat-killed gram-negative (G−) bacteria and subsequently reinfected with live pathogens. The innate immune responses against reinfection were evaluated through assessments of survival rates, antimicrobial peptide expression levels, and bacterial loads, complemented by transcriptomic and chromatin immunoprecipitation (ChIP) analyses. We found that flies trained with heat-killed gram-negative bacteria exhibited a higher survival rate upon secondary infection compared to unprimed flies, which was associated with increased expression of antimicrobial peptides. Priming with G− bacteria increased the sensitivity of the immune deficiency pathway to a second bacterial infection owing to lower levels of peptidoglycan recognition protein SC (PGRP-SC) after the first infection. The gut was the major tissue involved in the downregulation of PGRP-SC expression. The histone H3 lysine 9 trimethylation (H3K9me3) levels were higher at the PGRP-SC loci in immune-trained flies compared to untrained flies, contributing to the suppression of PGRP-SC expression. PGRP-SC overexpression in the fly gut abolished the effect of trained immunity. Taken together, our studies identify an innate immune memory in Drosophila that is regulated by gut-derived PGRP-SC through H3K9me3-mediated epigenetic repression of the PGRP-SC.
{"title":"PGRP-SC–mediated innate immune memory against pathogenic bacteria in Drosophila","authors":"Zihao Deng , Jiazhen Luo , Yufu Zhang , Chen Li , Shixin Deng , Jiazhi He , Zihao He , Wenqi Wu , Renjie Jiao , Jiyong Liu","doi":"10.1016/j.hlife.2025.09.003","DOIUrl":"10.1016/j.hlife.2025.09.003","url":null,"abstract":"<div><div>Trained immunity is essential for innate immune cells to retain a memory of previously encountered pathogens, strengthening the hosts’ response against these pathogens. However, the mechanisms governing trained immunity have not been well elucidated. In this study, flies of different genotypes were trained with heat-killed gram-negative (G<sup>−</sup>) bacteria and subsequently reinfected with live pathogens. The innate immune responses against reinfection were evaluated through assessments of survival rates, antimicrobial peptide expression levels, and bacterial loads, complemented by transcriptomic and chromatin immunoprecipitation (ChIP) analyses. We found that flies trained with heat-killed gram-negative bacteria exhibited a higher survival rate upon secondary infection compared to unprimed flies, which was associated with increased expression of antimicrobial peptides. Priming with G<sup>−</sup> bacteria increased the sensitivity of the immune deficiency pathway to a second bacterial infection owing to lower levels of peptidoglycan recognition protein SC (PGRP-SC) after the first infection. The gut was the major tissue involved in the downregulation of PGRP-SC expression. The histone H3 lysine 9 trimethylation (H3K9me3) levels were higher at the <em>PGRP-SC</em> loci in immune-trained flies compared to untrained flies, contributing to the suppression of PGRP-SC expression. PGRP-SC overexpression in the fly gut abolished the effect of trained immunity. Taken together, our studies identify an innate immune memory in <em>Drosophila</em> that is regulated by gut-derived PGRP-SC through H3K9me3-mediated epigenetic repression of the <em>PGRP-SC</em>.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 1","pages":"Pages 41-55"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145872154","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}
Pub Date : 2026-01-01DOI: 10.1016/j.hlife.2025.12.007
George Fu Gao
{"title":"From “Three” to all—A new chapter for hLife","authors":"George Fu Gao","doi":"10.1016/j.hlife.2025.12.007","DOIUrl":"10.1016/j.hlife.2025.12.007","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 1","pages":"Pages 1-2"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145872239","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}
Pub Date : 2026-01-01DOI: 10.1016/j.hlife.2025.05.010
Hui Zhang , Darong Hao , Yulu Gong , Yaqian Xu , Chongyu Ding , Jing Wang , Tongyan An , Yining Liu , Qiming Yin , Tianlang Tong , Xiangwei Li
{"title":"Associations of twelve DNA methylation algorithms of aging with mortality","authors":"Hui Zhang , Darong Hao , Yulu Gong , Yaqian Xu , Chongyu Ding , Jing Wang , Tongyan An , Yining Liu , Qiming Yin , Tianlang Tong , Xiangwei Li","doi":"10.1016/j.hlife.2025.05.010","DOIUrl":"10.1016/j.hlife.2025.05.010","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 1","pages":"Pages 56-58"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145872155","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}
Pub Date : 2026-01-01DOI: 10.1016/j.hlife.2025.09.004
Chibuike Ibe
{"title":"Increasing priority for antifungal resistance research—Are we making progress? An excerpt from GAMRIF summit 2025","authors":"Chibuike Ibe","doi":"10.1016/j.hlife.2025.09.004","DOIUrl":"10.1016/j.hlife.2025.09.004","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 1","pages":"Pages 59-62"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145872156","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}
Pub Date : 2025-12-01DOI: 10.1016/j.hlife.2025.05.014
Mengge Wang , Lintao Luo , Hui-Yuan Yeh , Chuan-Chao Wang , Huijun Yuan , Chao Liu , Renkuan Tang , Guanglin He
{"title":"Mighty oaks from little acorns: High-quality genomes of underrepresented populations enhance health equity in precision medicine","authors":"Mengge Wang , Lintao Luo , Hui-Yuan Yeh , Chuan-Chao Wang , Huijun Yuan , Chao Liu , Renkuan Tang , Guanglin He","doi":"10.1016/j.hlife.2025.05.014","DOIUrl":"10.1016/j.hlife.2025.05.014","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 12","pages":"Pages 621-625"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145772009","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}
Pub Date : 2025-12-01DOI: 10.1016/j.hlife.2025.10.003
Qian Zhao , Rui Ma , Kun Huang , Juan Wang , Donglin Zhang , Jingyuan Wang , Xiaofeng Ding , Feiyun Chen , Sijia Zhao , Na Ni , Xiaodie Zhang , Qian Du , Xiaojun Lin , Hua Wan , Jianglin Zhang , Xiaolei Ding , Shuang Yang , Fengping Xu , Yongxian Lai
Hair loss and graying, the earliest visible signs of skin aging, are driven by the functional decline of hair follicle stem cells and their niches. To elucidate the transcriptional mechanisms involved in scalp aging, we conducted a comprehensive analysis of human scalp samples using single-cell RNA sequencing and spatial transcriptomic technologies. Our study profiled the transcriptomes of 57,181 cells from scalp samples obtained from four young, six middle-aged, and one elderly individual. The integrated bioinformatic pipeline included cell clustering, spatial deconvolution, pseudotime trajectory, as well as cell-type specific gene expression, and intercellular communication analysis. An additional 92 volunteers were included, comprising 90 (37 young, 27 middle-aged, and 26 elderly) for trichoscopic examination, one young individual for senescence-associated β-galactosidase (SA-β-gal) staining, and one elderly individual for both MKI67 immunofluorescence and SA-β-gal staining. This approach led to several key findings: we identified three subtypes of mitotic keratinocytes that localized in the interfollicular epidermis (IFE), outer root sheath (ORS), and hair matrix, with pseudotime trajectory further confirming their transitional stage. Furthermore, in middle-aged scalps, we observed activated activator protein 1 (AP-1) transcription factor complex in keratinocytes, upregulated DCT gene in melanocytes, and decreased bone morphogenetic protein (BMP) and noncanonical wingless/integrated (ncWNT) signaling in dermal papilla (DP)–keratinocytes cross-talk. Due to the insufficient sample size and under-representation of elderly samples, transcriptional features associated with late aging, sex, and scalp regions were not completely captured. Nevertheless, our study provides valuable cell-resolved transcriptional insights into hair follicle aging and may support the development of future regenerative therapies.
{"title":"Single-cell RNA sequencing profiles age-related transcriptional landscapes in human hair follicle cells","authors":"Qian Zhao , Rui Ma , Kun Huang , Juan Wang , Donglin Zhang , Jingyuan Wang , Xiaofeng Ding , Feiyun Chen , Sijia Zhao , Na Ni , Xiaodie Zhang , Qian Du , Xiaojun Lin , Hua Wan , Jianglin Zhang , Xiaolei Ding , Shuang Yang , Fengping Xu , Yongxian Lai","doi":"10.1016/j.hlife.2025.10.003","DOIUrl":"10.1016/j.hlife.2025.10.003","url":null,"abstract":"<div><div>Hair loss and graying, the earliest visible signs of skin aging, are driven by the functional decline of hair follicle stem cells and their niches. To elucidate the transcriptional mechanisms involved in scalp aging, we conducted a comprehensive analysis of human scalp samples using single-cell RNA sequencing and spatial transcriptomic technologies. Our study profiled the transcriptomes of 57,181 cells from scalp samples obtained from four young, six middle-aged, and one elderly individual. The integrated bioinformatic pipeline included cell clustering, spatial deconvolution, pseudotime trajectory, as well as cell-type specific gene expression, and intercellular communication analysis. An additional 92 volunteers were included, comprising 90 (37 young, 27 middle-aged, and 26 elderly) for trichoscopic examination, one young individual for senescence-associated β-galactosidase (SA-β-gal) staining, and one elderly individual for both MKI67 immunofluorescence and SA-β-gal staining. This approach led to several key findings: we identified three subtypes of mitotic keratinocytes that localized in the interfollicular epidermis (IFE), outer root sheath (ORS), and hair matrix, with pseudotime trajectory further confirming their transitional stage. Furthermore, in middle-aged scalps, we observed activated activator protein 1 (AP-1) transcription factor complex in keratinocytes, upregulated <em>DCT</em> gene in melanocytes, and decreased bone morphogenetic protein (BMP) and noncanonical wingless/integrated (ncWNT) signaling in dermal papilla (DP)–keratinocytes cross-talk. Due to the insufficient sample size and under-representation of elderly samples, transcriptional features associated with late aging, sex, and scalp regions were not completely captured. Nevertheless, our study provides valuable cell-resolved transcriptional insights into hair follicle aging and may support the development of future regenerative therapies.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 12","pages":"Pages 626-646"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145772010","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}
Pub Date : 2025-12-01DOI: 10.1016/j.hlife.2025.09.001
Chongye Guo , Guomei Fan , Qi Chen , Shiwen Li , Min Li , Dongmei Liu , Juncai Ma , Linhuan Wu
{"title":"CHIKVdb: A comprehensive genomic resource for chikungunya virus surveillance and outbreak response","authors":"Chongye Guo , Guomei Fan , Qi Chen , Shiwen Li , Min Li , Dongmei Liu , Juncai Ma , Linhuan Wu","doi":"10.1016/j.hlife.2025.09.001","DOIUrl":"10.1016/j.hlife.2025.09.001","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 12","pages":"Pages 647-650"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145772011","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}
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