Cellular immunology最新文献

{"title":"Potential therapeutic strategies targeting efferocytosis for inflammation resolution and tissue repair in inflammatory bowel disease","authors":"Chaoquan Li ,&nbsp;Wanting Liu ,&nbsp;Aoni Fu ,&nbsp;Haotian Yang ,&nbsp;Guanghui Yi","doi":"10.1016/j.cellimm.2025.104957","DOIUrl":"10.1016/j.cellimm.2025.104957","url":null,"abstract":"<div><div>Efferocytosis, the process by which apoptotic cells (ACs) are recognized and cleared by phagocytes, is a critical mechanism in maintaining intestinal immune homeostasis and promoting the resolution of inflammation. Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic intestinal inflammation, wherein defective efferocytosis contributes to the accumulation of ACs, secondary necrosis, and sustained mucosal damage. This review delineates the molecular mechanisms underlying efferocytosis and systematically examines its functional roles across five key intestinal phagocytic cell types: macrophages, dendritic cells (DCs), neutrophils, intestinal epithelial cells (IECs), and Paneth cells (PCs). Particular emphasis is placed on the dysregulation of efferocytosis capacity in IBD pathogenesis and the consequences of impaired apoptotic cell clearance in both professional and non-professional phagocytes. Furthermore, we evaluate emerging therapeutic strategies designed to restore or enhance efferocytosis, including modulation of macrophage polarization, LC3-associated phagocytosis pathways, nanotechnology-enabled delivery systems, and stem cell-based interventions. A comprehensive understanding of cell-type-specific efferocytosis in the intestinal microenvironment offers promising directions for the development of targeted, inflammation-resolving therapies for IBD.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"411 ","pages":"Article 104957"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunity in children: How does it begin?","authors":"Simon Fillatreau","doi":"10.1016/j.cellimm.2025.104945","DOIUrl":"10.1016/j.cellimm.2025.104945","url":null,"abstract":"","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"411 ","pages":"Article 104945"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The NLRP3 Inflammasome in inflammatory diseases: Cellular dynamics and role in granuloma formation","authors":"Isadora M. de Oliveira ,&nbsp;Mariana M. Chaves","doi":"10.1016/j.cellimm.2025.104961","DOIUrl":"10.1016/j.cellimm.2025.104961","url":null,"abstract":"<div><div>The innate immune system recognizes pathogen-associated molecular patterns (PAMPs) and damage associated molecular patterns (DAMPs) through pattern recognition receptors (PRRs). Inflammasomes, cytoplasmic protein complexes, are activated in response to PAMPs and DAMPs, leading to the release of inflammatory cytokines such as IL-1β and IL-18. NLRP3 inflammasome is one of the best characterized inflammasomes and recently its activation has been associated with granuloma formation, structures that aggregate immune cells in response to infections, such as those caused by bacteria, fungi and parasites, and autoinflammatory diseases, such as sarcoidosis. Activation of NLRP3 inflammasomes in macrophages induces the release of cytokines that recruit immune cells, such as monocytes and lymphocytes, to the site of infection. Neutrophils, monocytes, T and B lymphocytes are important in the formation and maintenance of granulomas. Although NLRP3 plays a key role in the immune response, cell recruitment and granuloma formation, many aspects of its function in different cell types remain to be elucidated. In this review, we aim to outline the NLRP3 inflammasome not only as a protein complex that aids innate immune cells in combating intracellular pathogens but also as a platform with broader implications in orchestrating immune responses. This underexplored aspect of the NLRP3 inflammasome presents a novel perspective on its involvement in immunity. Thus, we review the current understanding of the role of the NLRP3 inflammasome in immune cell infiltration and its significance in the organization and formation of granulomas in inflammatory diseases.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"411 ","pages":"Article 104961"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The real-world impact of corticosteroid-associated adverse events in myasthenia gravis: A patient-reported survey analysis","authors":"Jinyi Yan ,&nbsp;Kalam Choi ,&nbsp;Peicai Fu,&nbsp;Mengge Yang,&nbsp;Jing Lin,&nbsp;Mengcui Gui,&nbsp;Yue Li,&nbsp;Bitao Bu,&nbsp;Zhijun Li","doi":"10.1016/j.cellimm.2025.104956","DOIUrl":"10.1016/j.cellimm.2025.104956","url":null,"abstract":"<div><h3>Background</h3><div>Corticosteroids are crucial for managing acute exacerbation symptoms and preventing relapses in myasthenia gravis (MG) patients.</div></div><div><h3>Methods</h3><div>Between April 15–30, 2024, 2368 online self - report questionnaires were distributed. Eventually, 444 MG patients who had received corticosteroid therapy completed the survey.</div></div><div><h3>Results</h3><div>Self-reported adverse events (AEs) were observed in 97.5 % of the respondents. Among them, 72.5 % (322 patients) reported experiencing more than four AEs. The quality of life (QOL) of patients with MG was significantly impacted, with average MG-QOL scores of 18.07 ± 12.03. Patients with a cumulative dosage exceeding 20 g experienced the highest incidence of various AEs compared to those with lower cumulative dosages (5–20 g and less than 5 g). Additionally, a longer duration of corticosteroid exposure was associated with a higher reported incidence of AEs. Cox risk regression modeling revealed that a longer disease course, a history of myasthenic crisis, and the average daily dose of steroids (exceeding 5 mg/d), were independent predictors of corticosteroid-associated AEs. The study revealed in a single MG center, the awareness of these AEs was low among Chinese patients.</div></div><div><h3>Conclusion</h3><div>This study systematically assessed the incidence and risk factors of corticosteroid-related AEs in Chinese MG patients. The study found that the occurrence of AEs was associated with the cumulative dosage and duration of corticosteroid use. Additionally, long disease duration, a history of myasthenic crises, and an average daily dosage exceeding 5 mg/d are identified as risk factors for corticosteroid-related AEs in patients with MG.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"411 ","pages":"Article 104956"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apelin-13 enhances neurofunctional recovery and suppresses neuroinflammation via the SIRT1/NF-κB axis in ischemic stroke","authors":"Zhe Peng ,&nbsp;Dewen Ru ,&nbsp;Guangpeng Leng ,&nbsp;Jinghua Peng ,&nbsp;Meng Zhang ,&nbsp;Bin Cai","doi":"10.1016/j.cellimm.2025.104958","DOIUrl":"10.1016/j.cellimm.2025.104958","url":null,"abstract":"<div><h3>Background</h3><div>Ischemic stroke is a major cause of mortality and disability, with neuroinflammation driving secondary brain injury. Microglial activation contributes to neuronal apoptosis, BBB disruption, and prolonged neurological deficits. Apelin-13, an endogenous peptide, has demonstrated neuroprotective potential, but its precise mechanisms remain unclear. This study investigates how Apelin-13 modulates neuroinflammation and the molecular pathways involved in ischemic stroke.</div></div><div><h3>Methods</h3><div>Mice underwent middle cerebral artery occlusion-reperfusion (MCAO/R) to model ischemic stroke, followed by Apelin-13 administration. Neurological function was assessed using Garcia scoring, adhesive removal, rotarod, and grid-walking tests. Infarct volume was quantified via TTC staining, and MRI evaluated cerebral edema. Immunofluorescence staining and Western blotting were used to assess neuronal apoptosis and BBB integrity. Microglial activation and polarization were analyzed via Iba1 co-immunostaining with CD16 (pro-inflammatory) and Arg1 (anti-inflammatory) markers. In vitro, primary microglia and BV2 cells were exposed to oxygen-glucose deprivation (OGD) to mimic ischemia, and Apelin-13's effects on inflammatory signaling were examined. The role of the SIRT1/NF-κB axis was evaluated using the SIRT1 inhibitor EX-527.</div></div><div><h3>Results</h3><div>Apelin-13 significantly improved post-stroke neurological function, reduced infarct volume, and alleviated cerebral edema. It preserved BBB integrity by reducing vascular leakage and albumin extravasation and suppressed neuronal apoptosis by downregulating cleaved caspase-3. Apelin-13 also mitigated neuroinflammation by decreasing microglial activation and shifting polarization toward an anti-inflammatory phenotype, as evidenced by reduced CD16+ and increased Arg1+ microglia. In vitro, Apelin-13 suppressed OGD-induced pro-inflammatory cytokine release while promoting anti-inflammatory responses. Mechanistically, Apelin-13 upregulated SIRT1, inhibiting NF-κB signaling and reducing inflammatory mediator expression. SIRT1 inhibition with EX-527 reversed these effects, restoring NF-κB activation and pro-inflammatory microglial polarization.</div></div><div><h3>Conclusions</h3><div>Apelin-13 exerts neuroprotective effects in ischemic stroke by preserving BBB integrity, reducing neuronal apoptosis, and suppressing neuroinflammation. These effects are mediated through SIRT1 activation and NF-κB inhibition. Targeting the Apelin-13/SIRT1/NF-κB axis may offer a promising therapeutic strategy for mitigating neuroinflammation and improving stroke recovery.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"413 ","pages":"Article 104958"},"PeriodicalIF":3.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144069955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lupeol mitigates spinal cord injury by modulating microglial M1/M2 polarization via Na+/K+-ATPase-mediated mitophagy","authors":"Ruyin Liu ,&nbsp;Zongjin Yue ,&nbsp;Jia'an Dong ,&nbsp;Cheng Zhang ,&nbsp;Chuanghao Guo ,&nbsp;Xinli Wang","doi":"10.1016/j.cellimm.2025.104955","DOIUrl":"10.1016/j.cellimm.2025.104955","url":null,"abstract":"<div><div>Spinal cord injury (SCI) often results in severe disability or even death, with inflammation playing a critical role in hindering recovery. Although Lupeol is known for its potent anti-inflammatory properties, its specific role in SCI-induced inflammation remains underexplored. In this study, an in vitro inflammation model was established using LPS-stimulated BV2 microglia. Lupeol treatment effectively counteracted LPS-induced reductions in Na⁺/K⁺-ATPase (NKA) activity, suppression of mitophagy, M1 polarization of microglia, release of inflammatory factors, and increased pyroptosis. Mechanistically, Lupeol alleviated microglial inflammation by enhancing mitophagy through the activation of NKA activity. Furthermore, Lupeol upregulated NKA activity and mitophagy by activating the AMPKα2-mTOR-TFEB pathway. In vivo, a mouse model of SCI was established, and Lupeol was administered daily via intraperitoneal injection. Lupeol treatment significantly reduced neuronal loss, promoted microglial polarization from the M1 to the M2 phenotype, attenuated inflammation, and improved motor function recovery in SCI mice. In conclusion, Lupeol promotes mitophagy by enhancing NKA activity via the AMPK–mTOR–TFEB pathway, thereby suppressing the pro-inflammatory phenotype of microglia and mitigating SCI progression.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"411 ","pages":"Article 104955"},"PeriodicalIF":3.7,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aged mice-derived bronchial epithelial cells regulate Th17 cell differentiation in asthma via the MBD2-sICOSL axis","authors":"Zhifeng Chen ,&nbsp;Yulin Shang ,&nbsp;Yu Yuan ,&nbsp;Xiaoying Ji ,&nbsp;Subo Gong ,&nbsp;Qingping Zeng ,&nbsp;Xudong Xiang","doi":"10.1016/j.cellimm.2025.104954","DOIUrl":"10.1016/j.cellimm.2025.104954","url":null,"abstract":"<div><div>Th17 cells are involved in the pathogenesis of elderly asthma. Bronchial epithelial cells (BECs) can act as antigen-presenting cells, and our previous studies have shown that methyl-CPG binding domain protein 2 (MBD2) in BECs can promote Th17 cell differentiation in asthma. However, the effect of BECs from different age groups (young and old) on Th17 cells remains unclear. In this study, BECs were co-cultured with CD4⁺ T cells, and it was found that BECs from young mice promoted the biased differentiation of Th2 cells, while BECs from older mice facilitated the biased differentiation of Th17 cells. Interestingly, MBD2 was highly expressed in BECs from older mice compared to BECs from young mice. MBD2 silencing induced inhibition of Th17 cell differentiation, while MBD2 overexpression reversed this change and promoted Th cell differentiation into Th17 cells. Soluble inducible T cell costimulator ligand (sICOSL) is mainly involved in the regulation of T cells after activation. In this study, we found that sICOSL levels were lower in BECs of old mice compared to BECs of young mice. Mechanistically, sICOSL levels increased with MBD2 silencing and decreased with MBD2 overexpression. As expected, the addition of anti-sICOSL antibodies significantly enhanced Th17 cell differentiation and suppressed Th2 cell differentiation, while exogenous sICOSL supplementation promoted Th2 cell differentiation and inhibited Th17 cell differentiation. However, neither anti-sICOSL nor exogenous sICOSL affected the expression of MBD2. Taken together, these results suggest that BECs from older mice regulate Th17 cell differentiation via the MBD2-sICOSL axis. These findings provide new insights into the pathogenesis of Th17-activated asthma in elderly patients.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"411 ","pages":"Article 104954"},"PeriodicalIF":3.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel and effective tandem CD38 and CD19 targeting CAR-T cells inhibit hematological tumor immune escape","authors":"Xiuying Liu ,&nbsp;Yaru Feng ,&nbsp;Zhiru Song ,&nbsp;Jingjing Liu ,&nbsp;Zhiqiang Luo ,&nbsp;Guohua Yu ,&nbsp;Jianxun Wang","doi":"10.1016/j.cellimm.2025.104950","DOIUrl":"10.1016/j.cellimm.2025.104950","url":null,"abstract":"<div><div>Targeting CD19 with chimeric antigen receptor (CAR)-T cells is clinically effective, but tumor immune escape and tumor recurrence still occur. Designing CAR-T cells that target multiple antigens simultaneously is a viable approach for inhibiting tumor immune escape, and promising findings have been reported. In this study, we designed new CD19 and CD38 dual-target CAR-T cells that are strongly cytotoxic to target cells expressing CD19 or CD38. <em>In vitro</em> studies, compared with single-target CAR-T cells or CD19/CD38 tandem (Tan) CAR-T cells, CD38/CD19 Tan CAR-T cells presented similar CAR expression, superior cytotoxicity and antigen-stimulated T-cell proliferation. <em>In vivo</em> studies, CD38/CD19 Tan CAR-T cells demonstrated the same efficacy and safety as single-target CAR-T. These CD19/CD38 Tan CAR-T cells are fully compatible with existing clinical-grade T-cell manufacturing procedures and can be implemented using current clinical protocols. In summary, our findings provide an effective solution to the challenge of tumor immune escape in anti-CD19 CAR-T-cell therapy.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"411 ","pages":"Article 104950"},"PeriodicalIF":3.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of CD44+CCR2+CD64−monocyte-derived macrophage in chronic rhinosinusitis with nasal polyps","authors":"Yuling Zhang ,&nbsp;Mengzhe Yang ,&nbsp;Yan Li ,&nbsp;Zaichuan Wang ,&nbsp;Shujian Zhang ,&nbsp;Limin Zhao ,&nbsp;Yingyue Liu ,&nbsp;Xinyi Li ,&nbsp;Xue Wang ,&nbsp;Feng Lan ,&nbsp;Luo Zhang","doi":"10.1016/j.cellimm.2025.104953","DOIUrl":"10.1016/j.cellimm.2025.104953","url":null,"abstract":"<div><div>Heterogeneity of monocyte-derived macrophages (MDMs) is gradually recognized in polyp tissue of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the contributions of MDM subsets for sustaining inflammation remain unclear. This study therefore aimed to characterize MDM subsets in polyp tissues and estimate their functions. We identified MDM subsets in polyp tissues by flow cytometry, and analyzed the correlation between the expression of these subsets and disease severity. We also explored the similarities and differences between tissue MDMs and classical <em>ex vivo</em> polarized MDMs. By using appropriate substitutes for tissue MDMs, we investigated the function of MDMs. MDM1 (lin⁻CD44⁺CD64⁺) and MDM3 (lin⁻CD44⁺CCR2⁺CD64⁻) were identified in polyp tissues by flow cytometry. Recurrent CRSwNP patients exhibited higher levels of MDM3 compared to non-recurrent patients. This increase in MDM3 was positively correlated with the Lund-Mackay score, the number of infiltrated tissue eosinophils, and IL-5 expression levels. <em>Ex vivo</em> polarized alternatively activated (M2a) macrophage preferentially expressed MDM3 marker genes, which can be used as the substitute for MDM3 within the polyp tissues. M2a macrophages engulfed more <em>Staphylococcus aureus</em> than classically activated (M1) macrophages. However, interferon lambda 1 (IFN-λ1) did not alter the bacterial killing efficiency of M2a macrophages, nor did it affect the activation of reactive oxidase substrate (ROS) and signal transducer and activator of transcription 1 (STAT1) pathway and viability. The increase in MDM3 within polyp tissues, similar to classical M2a macrophages, acted as bacterial reservoirs and contributed to persistent inflammation, offering insights into the underlying mechanisms of CRSwNP.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"411 ","pages":"Article 104953"},"PeriodicalIF":3.7,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transfer of bone marrow niche-residential regulatory T cells ameliorates experimental colitis","authors":"Chen Meng ,&nbsp;Tatsuyuki Sato ,&nbsp;Ryosuke Ueda ,&nbsp;Jiwoo Kim ,&nbsp;Maria Serena Longhi ,&nbsp;Joji Fujisaki","doi":"10.1016/j.cellimm.2025.104952","DOIUrl":"10.1016/j.cellimm.2025.104952","url":null,"abstract":"<div><h3>Background</h3><div>Adoptive transfer of regulatory T cells (Tregs) has been proposed as a next-generation treatment approach for the treatment of various inflammatory or autoimmune disorders(Amini et al., 2022; Bluestone et al., 2023, 2015; Dall'Era et al., 2019; Chandran et al., 2017; Laukova and Glatman Zaretsky, 2023; Voskens et al., 2023; Canavan et al., 2016^1–8), inclusive of inflammatory bowel diseases (IBD). Identification of the appropriate Treg populations as donor sources for effective cell therapy is of great importance. We have recently identified specialized Tregs that localize within the hematopoietic stem cell (HSC) microenvironments(Fujisaki et al., 2011; Hirata et al., 2018, 2019, 2015; Kakiuchi et al., 2021a, 2021b; Furuhashi et al., 2025^9–16) of bone marrow (BM), termed HSC niches. These BM niche Tregs exhibit robust anti-inflammatory and pro-regenerative effects and render HSCs immune privileged. The transfer of BM niche Tregs exhibits high therapeutic effects against BM transplantation and injury(Hirata et al., 2018; Kakiuchi et al., 2021b^{10, 14)}. Yet, the treatment effects of transferred BM niche Tregs in non-BM disease settings remain unknown.</div></div><div><h3>Objectives</h3><div>We investigated the therapeutic effects of transfer of BM niche Tregs for IBD using mouse models of experimental colitis. To identify the key effector molecule of niche Tregs, we further examined the roles of cell-surface ectoenzyme CD39 expressed at high levels by BM niche Tregs.</div></div><div><h3>Study Design</h3><div>Mouse colitis was induced by administering dextran sulfate sodium salt. Subsequently, the mice received intravenous injections of BM niche Tregs, BM non-niche Tregs, lymph node Tregs, or vehicle alone. We compared these treatment effects on clinical scores, histopathological features and profiles of immune cells. We also tested how targeted deletion of CD39 in the adoptively transferred Tregs impacted experimental outcomes.</div></div><div><h3>Results</h3><div>The transfer of as few as 1.5 × 10⁴ BM niche Tregs per mouse ameliorated clinical and histopathological features of the mouse colitis far better than the transfer of other Tregs. The transfer of BM niche Tregs inhibited the generation of Th17 cells and promoted the regeneration and recovery of the colon tissue. Targeted deletion of CD39 in Tregs abrogated therapeutic effects of transferred BM niche Tregs.</div></div><div><h3>Conclusion</h3><div>We show robust therapeutic effects of the transfer of BM niche Tregs in the experimental model of colitis. Donor niche Tregs mediate anti-inflammatory and pro-regenerative effects via Treg CD39. Our work suggests the transfer of BM niche Tregs is a promising approach to treat colitic disorders and boost tissue regeneration.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"411 ","pages":"Article 104952"},"PeriodicalIF":3.7,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}