Inflammation and regeneration最新文献

{"title":"Effects of intranasal long-acting insulin pretreatment on postoperative delirium and the NLRP3/caspase-1/IL-1β pathway in older patients with esophageal cancer.","authors":"Yong Zhang, Wei Wu, Zuling Zhong, Yinghai Liu, Gu Gong, Qingqing Huang","doi":"10.1186/s41232-026-00418-4","DOIUrl":"10.1186/s41232-026-00418-4","url":null,"abstract":"<p><strong>Background: </strong>Insulin exhibits neuroprotective and anti-inflammatory properties. Preoperative intranasal insulin preconditioning is a potential strategy to prevent postoperative delirium (POD), but prior studies mainly used rapid-acting formulations. This investigation focused on intranasal long-acting insulin, which ensures sustained central nervous system exposure, in elderly patients undergoing radical esophagectomy. We assessed its impact on POD incidence and the NLRP3/caspase-1/IL-1β pathway.</p><p><strong>Methods: </strong>Sixty older patients scheduled for elective radical esophagectomy were randomized into two groups. The intervention group (n = 30) received a single intranasal dose of long-acting insulin (30 U) 1 day preoperatively, while the control group (n = 30) received an equivalent volume of physiological saline. POD was evaluated using the Confusion Assessment Method for the ICU on postoperative days 1, 2, and 3. Peripheral blood samples were collected before surgery and postoperatively to measure IL-1β concentrations and NLRP3/caspase-1 mRNA expression in mononuclear cells.</p><p><strong>Results: </strong>Compared to controls, long-acting insulin pretreatment significantly reduced POD incidence (16.7% vs. 46.7%, P = 0.012) and suppressed the postoperative rise in peripheral IL-1β levels (P < 0.05). In addition, NLRP3 and caspase-1 mRNA expression were notably lower in the insulin group during the postoperative period (P < 0.05). Correlation analysis revealed that in the control group, increases in NLRP3 mRNA, caspase-1 mRNA, and IL-1β levels on postoperative day 1 were significantly associated with the development of POD (P < 0.05). In contrast, no such significant correlations were found in the insulin intervention group.</p><p><strong>Conclusion: </strong>Preoperative intranasal long-acting insulin effectively decreases POD incidence in the first 3 days after radical esophagectomy in older patients. This protective effect may be associated with the observed sustained downregulation of the peripheral NLRP3/caspase-1/IL-1β signaling pathway, which consequently weakens the link between early postoperative inflammation and delirium. This emphasizes the advantage of long-acting formulations for continuous neuroprotection during the critical postoperative phase.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147719283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging roles of microRNAs and other non-coding transcriptome in muscular dystrophies.","authors":"Farah Gamal Abdelrehim, Zade Sadek, Salma A Fahim, Nada El-Ekiaby, Ahmed Ihab Abdelaziz, Injie Omar Fawzy","doi":"10.1186/s41232-026-00415-7","DOIUrl":"10.1186/s41232-026-00415-7","url":null,"abstract":"<p><p>Muscular dystrophies (MDs) are a set of neuromuscular diseases characterized by progressive muscle weakness and wasting. Their pathophysiology entails several aberrant genetic pathways including the perturbation of microRNA (miRNA) and other non-coding RNA (ncRNA) levels and functions, and the subsequent dysregulation of their downstream targets. In healthy tissue, ncRNAs exert their influence by fine-tuning physiological mechanisms. However, in dystrophic conditions, these ncRNAs become involved in modulation of pathological mechanisms. The main pathomechanism themes that involve ncRNAs and proteins in MD are myogenesis insufficiency, structural instability, destructive pathways, and signaling failure. This review attempts to delineate all the major contributory ncRNAs, particularly miRNAs, as well as their associated proteins involved in disease initiation, maintenance, and outcomes across the spectrum of MD subtypes.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13072657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147655648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-related downregulation of dihydrotestosterone-inactivating enzymes in human scalp sebaceous glands.","authors":"Yasuaki Ikuno, Yukie Kande, Akiko Arakawa, Akihiko Yamaguchi, Toshifumi Takahashi, Noriki Fujimoto, Hayato Naka-Kaneda","doi":"10.1186/s41232-026-00417-5","DOIUrl":"10.1186/s41232-026-00417-5","url":null,"abstract":"<p><strong>Background: </strong>Aging alters the systemic steroid environment, including reductions in circulating androgens. In peripheral tissues, androgen exposure is regulated mainly by local steroid metabolism, which can activate or inactivate androgens independently of systemic concentrations. In the scalp, 5α-reductase-mediated generation of dihydrotestosterone (DHT) has been studied extensively in relation to conditions such as androgenetic alopecia. In contrast, age-related regulation of DHT-inactivating pathways, including the aldo-keto reductase family 1 member C (AKR1C) family, remains insufficiently defined.</p><p><strong>Methods: </strong>We examined AKR1C1-4 expression in scalp tissues from individuals of different ages, sexes, and hair loss conditions using immunohistochemistry (IHC), quantitative PCR (qPCR), and reanalysis of publicly available RNA-sequencing (RNA-seq) datasets. Androgen receptor (AR) localization was assessed in multiple scalp compartments. AKR1C expression was also analyzed in immortalized human sebaceous gland cells (SEB-1) and dermal papilla cells (DPCs). In addition, the effect of sulforaphane on AKR1C expression was evaluated.</p><p><strong>Results: </strong>AKR1Cs were strongly expressed in male sebaceous glands (SGs) but declined with age. AKR1C4, previously considered liver specific, was detected in SGs and hair follicles (HFs) by IHC and further confirmed by qPCR in SEB-1 cells and DPCs. AR expression was predominant in SGs, with lower levels in sweat glands, the epidermal granular layer, and the HF infundibulum, but not detected in dermal papillae and bulge regions. AR localization was cytoplasmic in the epidermis but nuclear in SGs and sweat glands, and was unaffected by age, sex, or hair loss condition. Sulforaphane treatment upregulated AKR1C expression in both SEB-1 cells and DPCs.</p><p><strong>Conclusions: </strong>We identify scalp SGs as a principal site of AR expression and AKR1C-mediated androgen inactivation, including AKR1C4, and demonstrate that AKR1C expression in SGs is sex dependent and declines with age. These findings suggest that age-associated changes in SG steroid metabolism may influence local androgen metabolism within the scalp microenvironment, with implications for HF homeostasis during aging.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147629554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A spatiotemporal atlas of senescence-associated secretory phenotype in fracture healing: stage-dependent mechanisms and therapeutic windows.","authors":"Binyu Chen, Gan Li, Qihang Fang, Peng Ding, Youshui Gao","doi":"10.1186/s41232-026-00416-6","DOIUrl":"10.1186/s41232-026-00416-6","url":null,"abstract":"<p><p>Fracture repair remains a significant clinical challenge in orthopedics, particularly in aging populations. Accumulating evidence indicates that cellular senescence critically modulates the fracture microenvironment via the senescence-associated secretory phenotype (SASP). The SASP constitutes a complex secretory program of senescent cells that releases pro-inflammatory cytokines, growth factors, and matrix-modifying enzymes to reshape the surrounding microenvironment. Rather than being a random collection of molecules, the SASP represents a coordinated signaling network that can either promote tissue repair or drive chronic inflammation depending on its context. In this review, we apply a systematic SASP classification to the canonical four phases of fracture healing to clarify their distinct roles across these stages. During the inflammatory phase, SASP-associated (but non-exclusive) inflammatory cytokines and chemokines potentiate innate immune cell recruitment and early host defense, thereby initiating the repair cascade; in the soft-callus phase, chemotactic and angiogenic SASP components (such as CCL2, PDGF, VEGF) position mesenchymal progenitors and support chondrogenesis and neovascularization; in the hard-callus phase, osteoinductive growth factors and matrix-acting proteases (such as TGF-β, IGFBPs, MMP-9/13) promote cartilage-to-bone conversion and early mineral deposition; and in the remodeling phase, regulated SASP-mediated matrix changes couple osteoclast resorption with osteoblast formation, while sustained pro-inflammatory or profibrotic signals may hinder the fine remodeling of the structure. This stage-resolved framework elucidates the dual nature of SASP, with transient activation facilitating repair and sustained overproduction leading to impaired remodeling. This framework provides a conceptual basis for developing stage-specific interventions to enhance bone repair. Notably, many mediators discussed here overlap with the broader injury-induced inflammatory secretome and are not senescence-exclusive; where possible, we emphasize senescent-cell-enriched contributions and regulatory circuits rather than implying unique cellular origins.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13085506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147583327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural killer cells: gatekeepers of healthy aging in longevity medicine.","authors":"Joanna Y Yang, Doris T Tu, Jun-Cheng Liao, Oscar K Lee","doi":"10.1186/s41232-026-00414-8","DOIUrl":"10.1186/s41232-026-00414-8","url":null,"abstract":"<p><p>Natural killer (NK) cells are innate lymphocytes that provide rapid immune surveillance through the recognition and elimination of virally infected, malignant, and stressed cells. Beyond their established roles in host defense, accumulating evidence indicates that NK cells undergo profound age-associated remodeling affecting subset distribution, receptor balance, metabolic programming, and effector function. These changes, collectively referred to as NK immunosenescence, contribute to impaired clearance of senescent cells, dysregulated inflammation, and increased susceptibility to cancer, infection, and metabolic disease. In this review, we integrate current knowledge of NK cell aging into the emerging framework of longevity medicine. Rather than introducing NK cells as a newly identified determinant of aging, we synthesize evidence positioning them as key immune effectors whose functional state reflects and influences biological aging processes. We highlight how NK cells participate in senescence surveillance, tissue homeostasis, and immunometabolic regulation across organs, and how their dysfunction intersects with multiple hallmarks of aging. We further discuss the potential utility of NK-related phenotypic and functional metrics as complementary biomarkers of immune aging, while acknowledging current limitations in specificity and prognostic validation. Finally, we examine therapeutic strategies aimed at preserving or restoring NK competence, ranging from lifestyle and nutritional interventions to cytokine-based therapies, immune checkpoint modulation, and emerging cellular platforms. While many advanced NK-targeted approaches remain investigational-particularly outside oncology settings-we outline a translational roadmap linking NK biology to actionable interventions and measurable outcomes relevant to healthspan. By situating NK cells within a systems-level view of immune aging, this review frames them as a tractable component of precision longevity medicine rather than a singular regulator of aging.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147517566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune molecular mechanisms of PANoptosis in sepsis-induced acute kidney injury.","authors":"Jie Zheng, Jian Lan, Ze-Yu Zhao, Liang Luo, Xi-Jiang Zhang, Qiong-Ying Hu","doi":"10.1186/s41232-026-00412-w","DOIUrl":"10.1186/s41232-026-00412-w","url":null,"abstract":"<p><p>Sepsis-induced acute kidney injury (S-AKI) is a common, life-threatening clinical complication with complex, incompletely understood pathophysiological mechanisms. Historically, the three main types of regulated cell death (RCD) were necroptosis, apoptosis, and pyroptosis. Recent discoveries of significant molecular overlap between these pathways have suggested that PANoptosis represents a combined inflammatory RCD mechanism. Accumulating evidence suggests that PANoptosis contributes to the progression of S-AKI. To clarify underlying mechanisms and guide innovative therapeutic methods, this review summarizes recent findings on the pathogenesis of S-AKI, with an emphasis on the growing significance of PANoptosis'.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147482742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amphiregulin attenuates sepsis-induced myocardial dysfunction by maintaining the localization of connexin43.","authors":"Man Chen, Shinnosuke Takamori, Koichi Isayama, Yuqing Wang, Shuntaro Matsunaga, Sayoko Narahara, Masanori Honsho, Masaharu Murata, Shintaro Kinugawa, Kohtaro Abe, Tomohiko Akahoshi","doi":"10.1186/s41232-026-00410-y","DOIUrl":"10.1186/s41232-026-00410-y","url":null,"abstract":"<p><strong>Background: </strong>Sepsis-induced myocardial dysfunction (SIMD) is a prevalent complication among septic patients, significantly worsening patient prognosis and elevating the mortality rate. Connexin 43 (Cx43), a pivotal cardiac gap junction protein, maintains cardiac function, and its disarrangement is closely linked to cardiac diseases. However, the role of Cx43 localization changes in SIMD remains unclear. Amphiregulin (AREG) was recently reported to promote the recovery of Cx43 disarrangements. This research aimed to explore the role of Cx43 in SIMD and the preventive potential of AREG.</p><p><strong>Methods: </strong>A mouse model of SIMD was induced using lipopolysaccharide (LPS) and treated with AREG. Cardiac function and electrical conduction were assessed using echocardiography and an electrocardiogram. Inflammatory responses, Cx43 regulation, and related signaling pathways were further investigated in serum and cardiac tissues. Relevant signal pathway analysis was investigated in cultured cardiomyocytes.</p><p><strong>Results: </strong>LPS administration significantly reduced cardiac ejection fraction and left ventricular fractional shortening, which were accompanied by disorganization, fragmentation, and lateralization of Cx43 at 6 h. These pathological alterations were associated with increased phosphorylation of p^S368-Cx43, mediated by p38 activation. AREG pretreatment improved cardiac function and QRS interval, and preserved Cx43 localization at intercellular discs, along with p^S368-Cx43 phosphorylation with reduction of p38 inhibition. Myocardial cell studies confirmed that AREG inhibited p38 phosphorylation, independent of AKT, in LPS-induced cardiac dysfunction.</p><p><strong>Conclusion: </strong>This study highlights the role of Cx43 phosphorylation in SIMD and demonstrates the preventive potential of AREG in SIMD, which is associated with a reduction in p38 activation and a decrease in the phosphorylation level of p^S368-Cx43. These findings may provide a novel therapeutic target for SIMD.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13020034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147391922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breaking the cycle of excitotoxicity: blood glutamate scavenging provides robust neuroprotection in spinal cord injury.","authors":"Josef Levin, Yona Goldshmit, Rosemary Lavender, Alex Yakovchuk, Evgeni Banyas, Ruth Baltovska, Amit Benbenishty, Angela Ruban","doi":"10.1186/s41232-026-00411-x","DOIUrl":"10.1186/s41232-026-00411-x","url":null,"abstract":"<p><strong>Background: </strong>Spinal cord injury (SCI) triggers a rapid and sustained cascade of secondary damage, with glutamate (Glu) excitotoxicity recognized as a central mechanism driving neuronal death and functional decline. Despite extensive research, no effective therapy targeting excitotoxicity, and no neuroprotective treatment in general, is currently available. This highlights the urgent need for novel and effective therapeutic strategies for managing SCI.</p><p><strong>Methods: </strong>We developed a combined blood-glutamate scavenging (cBGS) therapeutic platform comprising two recombinant enzymes (rGOT1 and rGPT1), their respective co-substrates (oxaloacetate and pyruvate), and the cofactor pyridoxal phosphate (PLP). The efficacy of cBGS was evaluated in mouse and rat models of moderate-to-severe spinal cord compression and contusion injury. Glutamate concentrations were quantified in blood and cerebrospinal fluid (CSF), while histological and functional outcomes were assessed from 1 day to 7 weeks post-injury to determine neuroprotective efficacy.</p><p><strong>Results: </strong>Systemic cBGS administration significantly reduced Glu concentrations in both blood and CSF, leading to a marked reduction in apoptosis, neuroinflammation, demyelination, and glial scarring, while promoting neuronal and axonal survival. Treated animals demonstrated substantial locomotor recovery, up to 80% improvement in performance. Notably, cBGS remained effective when administered up to eight hours post-injury, indicating a clinically relevant therapeutic window and excellent safety profile. Core findings were independently validated in a rat severe compression model performed by an external Contract Research Organization (CRO).</p><p><strong>Conclusions: </strong>The cBGS platform represents a first-in-class systemic neuroprotective therapy that effectively mitigates glutamate excitotoxicity and secondary injury following SCI. Its robust efficacy, wide therapeutic window, and favorable safety profile support its strong potential for clinical translation in acute SCI and other excitotoxicity-driven neurotrauma conditions, where no effective treatments currently exist.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13001199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147313748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced nerve regeneration after transplantation of NCAM-positive neural crest-like cells derived from human iPSC.","authors":"Tsuyoshi Amemiya, Takehito Ouchi, Hiroo Kimura, Kentaro Okuyama, Thinh Quang Phan, Takuji Iwamoto, Taneaki Nakagawa, Morio Matsumoto, Masaya Nakamura, Hideyuki Okano, Narihito Nagoshi, Shinsuke Shibata","doi":"10.1186/s41232-026-00409-5","DOIUrl":"10.1186/s41232-026-00409-5","url":null,"abstract":"<p><strong>Background: </strong>Peripheral nerve injuries often cause persistent sensory and motor deficits, and autologous nerve grafting, the current standard, is limited by donor site morbidity and tissue availability. Human induced pluripotent stem cells (hiPSCs)-derived neural crest-like cells (NCLCs) have shown potential for nerve regeneration, but achieving high purity and safety remains a challenge.</p><p><strong>Methods: </strong>Using a mouse model of large sciatic nerve defects, we evaluated the efficacy of transplanting NCLCs triple-positive for low-affinity nerve growth factor receptor (LNGFR), thymocyte antigen 1 (THY-1), and neural cell adhesion molecule (NCAM). Purified triple-positive cells induced from hiPSC-derived neural crest lineage were seeded in the conduit with collagen gel in the transplantation group and compared the regeneration with the autograft group and the negative control group without cells.</p><p><strong>Results: </strong>NCAM-positive NCLCs promoted robust angiogenesis and recruited host Schwann cells, thereby establishing a supportive regenerative microenvironment. This facilitated axonal regrowth, thick myelination, and organized nerve architecture comparable to that of autografts. Functional recovery, assessed by electrophysiological conduction and motor performance, eventually matched autografts, with earlier improvement observed in the transplantation group. No tumor formation was detected, and the proliferative activity of transplanted cells declined over time. Selective marker-based purification likely contributed to the favorable safety profile.</p><p><strong>Conclusion: </strong>NCAM-positive NCLCs derived from hiPSCs enhance peripheral nerve regeneration through vascularization and Schwann cell-mediated remyelination, resulting in structural and functional recovery equivalent to autografts. This strategy offers a safe, scalable alternative to donor nerve harvest, and integration with bioengineered conduits could further expand clinical applicability in peripheral nerve reconstruction.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12934083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146168380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Granzyme A-producing type 1 innate lymphoid cells promote salivary secretion in the aged submandibular gland.","authors":"Hiroaki Abe, Erika Yamashita, Daisuke Okuzaki, Masaru Ishii","doi":"10.1186/s41232-026-00407-7","DOIUrl":"10.1186/s41232-026-00407-7","url":null,"abstract":"<p><strong>Background: </strong>Salivary gland function declines with age, contributing to periodontitis and aspiration pneumonia. However, the cellular mechanisms that preserve secretion during aging remain unclear.</p><p><strong>Methods: </strong>Mice were stratified by aging stage, and saliva output and tissue histology were assessed. To infer cell-cell communication, regions surrounding lymphocyte clusters were microdissected and subjected to site-specific single-cell RNA sequencing. Epithelial cell responses were evaluated in a coculture system using a neutralizing antibody. Finally, physiological relevance was assessed by in vivo depletion, followed by quantification of changes in saliva secretion.</p><p><strong>Results: </strong>Saliva production was maintained or modestly increased during early aging stages and coincided with the emergence of lymphoid cell clusters. Single-cell and interactome analyses identified Gzma + ILC1 subsets enriched in aged lymphoid cluster regions and predicted crosstalk with epithelial cells via a GZMA-Pard3 axis. Upregulation of epithelial Aqp5 expression was confirmed in vitro. In vivo depletion of ILC1s in aged mice significantly reduced stimulated saliva output, indicating that local ILC1-derived GZMA supports secretory capacity.</p><p><strong>Conclusions: </strong>Aged submandibular salivary glands accumulated ILC1s that promote epithelial function through a GZMA-dependent pathway and increased AQP5 expression, thereby maintaining salivary secretion during early aging. These findings identify ILC1s as regulators of salivary gland homeostasis and highlight the GZMA-Pard3 axis as a potential therapeutic target.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12930742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147277741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}