Cellular Immunology[JOURNAL]
Sun
200 papers
Efficacy and safety of interferon alpha-2b aerosol therapy for patients infected with the SARS-CoV-2 omicron variant: A randomized controlled single-blind study.
Jin Y, Meng X, Qian Z … +4 more , Zhao J, Lv Y, Ling Y, Fan X
Cell Immunol · 2025 Aug · PMID 40555084 · Publisher ↗
The efficacy of Type I interferon (IFN) in treating COVID-19 has remained controversial. In this study, we conducted a randomized, single-blind clinical trial to evaluate the efficacy of recombinant human interferon alph...
The efficacy of Type I interferon (IFN) in treating COVID-19 has remained controversial. In this study, we conducted a randomized, single-blind clinical trial to evaluate the efficacy of recombinant human interferon alpha 2b (IFN-alpha2b) in treating COVID-19 patients during the Omicron outbreak in Shanghai in 2022. The study cohort included 505 patients, classified as asymptomatic, mild, or moderate based on clinical symptoms. The cohort was divided into an experimental group, which received a 7-day course of nebulized inhalation of IFN-alpha2b, and a control group, which received an identical treatment course using physiological saline in place of IFN-alpha2b. Effectiveness and safety were assessed by measuring the length of hospital stay, improvement in clinical symptoms, and occurrence of adverse events. While there were no significant differences in overall hospital stay or symptom improvement between the two groups, IFN-alpha2b treatment was associated with a significantly shorter hospitalization time in the asymptomatic subgroup. Multivariate Cox regression analysis identified IFN nebulization therapy as a positive predictor of discharge within 12 days, alongside the white blood cell count at admission, and the IL-4 level at admission as a potential negative predictor. Regarding safety, there was no significant difference in the incidence of adverse reactions between the two groups during treatment. Collectively, our study suggests that Type I IFN, when administered via nebulized inhalation, may offer benefits specifically for the asymptomatic subgroup among COVID-19 patients, indicating selective efficacy.
MEX3A activates the JAK-STAT pathway to suppress NK cell cytotoxicity and accelerate lung adenocarcinoma progression.
Peng J, Yan H, Zhou W … +3 more , Chen H, Xu T, He C
Cell Immunol · 2025 Aug · PMID 40554097 · Publisher ↗
BACKGROUND: Therapeutic potential of natural killer (NK) cells is recognized in treating lung adenocarcinoma (LUAD), but impairment of NK cell functions in various cancers weakens anti-tumor capabilities. Uncovering mole...
BACKGROUND: Therapeutic potential of natural killer (NK) cells is recognized in treating lung adenocarcinoma (LUAD), but impairment of NK cell functions in various cancers weakens anti-tumor capabilities. Uncovering molecular mechanisms is imperative for fortifying NK cells against degradation and for enhancing their cancer-inhibiting functions. METHODS: TCGA-LUAD database complemented by qRT-PCR presented MEX3A expression in LUAD. TIMER was employed to explore relationship between MEX3A levels and NK cell infiltration. In the co-culture system of LUAD and activated NK92 cells, CytoTox 96® assay was applied to gauge NK cell cytotoxicity. ELISA was used to quantify IFN-γ, Perforin, and Granzyme B in the supernatant. Flow cytometry assessed LUAD cell apoptosis. Single-gene enrichment analysis of MEX3A was performed with KEGG database. Western blot examined protein expression in JAK-STAT signaling. In vivo studies validated the role of MEX3A expression on tumorigenesis. RESULTS: MEX3A was upregulated in LUAD tissue and cells, negatively linked to NK cell infiltration levels. Gene set enrichment analysis pointed to influences of MEX3A expression on dynamics of JAK-STAT signaling. MEX3A overexpression in LUAD cells impaired NK cell cytotoxicity and cell apoptosis, and these effects were reversible by a JAK pathway inhibitor. Mouse studies illustrated that LUAD progression was curbed by MEX3A suppression, alongside an enhanced presence of NK cells within tumor microenvironment. CONCLUSION: To synthesize our results, this study identified that MEX3A in LUAD promoted malignancy of the disease by enhancing JAK-STAT signaling, which in turn inhibited cytotoxic capabilities of NK cells, thus providing novel insights for LUAD immunotherapy.
Curcumin mitigates systemic lupus erythematosus by suppressing double-negative T cells through cell apoptosis.
Xu M, Li X, Bao C … +5 more , Zhang Y, Yang J, Hang Y, Sun L, Chen H
Cell Immunol · 2025 Aug · PMID 40532482 · Publisher ↗
OBJECTIVE: Curcumin extracted from the rhizome of Curcuma longa has anti-inflammatory, antioxidant and antitumour properties. In previous studies, curcumin has been reported to have therapeutic effects on systemic lupus...
OBJECTIVE: Curcumin extracted from the rhizome of Curcuma longa has anti-inflammatory, antioxidant and antitumour properties. In previous studies, curcumin has been reported to have therapeutic effects on systemic lupus erythematosus (SLE), in which the upregulation of double-negative T (DNT) cells was detected. Therefore, the purpose of this study is to explore the role of curcumin in the remission of SLE by regulating DNT cell homeostasis. METHODS: Two established murine models of lupus, MRL/lpr mice and R848-induced mice, were administered with 50 mg/kg curcumin to evaluate its therapeutic effects. Flow cytometry was used to detect the proportions of DNT cells, Treg cells and Th cells in mouse tissues. H&E staining and immunofluorescence were used to assess inflammatory cell infiltration and immune complex deposition in the kidney. Enzyme-linked immunosorbent assay (ELISA) and real-time quantitative PCR (RT-qPCR) were used to detect the expression of inflammatory factors. RNA sequencing was used to identify differentially expressed genes and explore regulatory mechanisms, and western blot was used to detect protein expression. RESULTS: Our results suggest that the accumulation of DNT cells is closely associated with lupus pathogenesis and development in both mouse models, whereas curcumin treatment can improve lupus serological and immunological profiles, and regulate T-cell homeostasis, especially DNT cells. Further studies demonstrated that curcumin promoted DNT cell apoptosis to eventually decrease the accumulation of DNT cells. CONCLUSION: Curcumin can improve lupus serological and immunological profiles as well as renal pathology by suppressing DNT cells, and may be a potential candidate for the treatment of SLE.
A novel approach to hematopoietic stem cell transplantation: The effect of CMV infection and HLA genotypes on chimerism status in Egyptian patients.
Ghorab RM, Talkhan HA, ElGwad AMA … +3 more , Radwan RA, Abdelwahab HEE, Abd El Aziz DM
Cell Immunol · 2025 Aug · PMID 40517559 · Publisher ↗
Several studies have investigated the association between HLA alleles and cytomegalovirus (CMV) infection following hematopoietic stem cell transplantation (HSCT). It was found that many HLA alleles were associated with...
Several studies have investigated the association between HLA alleles and cytomegalovirus (CMV) infection following hematopoietic stem cell transplantation (HSCT). It was found that many HLA alleles were associated with increased rate of CMV infection, while others had a protective effect against infection. However, to our knowledge no studies have investigated the effect of this relation on chimerism status post transplantation. Previous results concluded that CMV reactivation or infection increases conversion from mixed chimerism toward complete chimerism (CC) as a consequence of concomitant activation of immune system. Our aim is to study the association of CMV and certain HLA alleles and their effect on chimerism status post transplantation and identify other factors affecting chimerism status. 165 patients who underwent allogeneic HSCT for different hematological indications were studied. Both recipients (R) and donors (D) underwent serological testing for CMV-specific IgG and IgM, HLA typing, and chimerism analysis. CMV infection or reactivation was assessed in recipients through weekly monitoring of CMV DNA. Patients were followed up for 100 days where chimerism analysis was performed at 28, 60, 90, and 100 days post-transplantation. Eighty-five patients were positive for CMV by PCR post transplantation while eighty patients were CMV negative. Acute graft versus host disease (aGvHD) was significantly increased in CMV positive patients. Multivariate analysis (MVA) has indicated that HLA-A*2, HLA-B*14, HLA-B*41, HLA-DRB1*04 and HLA-DRB1*13, as well as a diagnosis of myelodysplastic syndrome and bone marrow aplasia, significantly increased the risk for CMV positivity post transplantation. HLA-DRB1*11 positivity was associated with a higher rate of aGvHD. CMV infection/reactivation as indicated by positive CMV PCR post-transplant was associated with a faster rate of conversion toward CC, and this effect was independent of the implemented conditioning regimen or the presence of aGvHD. Additionally, D+/R- transplant setting was significantly associated with early CC. On MVA, CMV reactivation was associated with acceleration of conversion toward CC, while HLA-A*33, HLA-DRB1*13, HLA-DRB1*15 and D-/R+ transplant setting were factors associated with delayed CC. In conclusion, CMV infection/reactivation and D+/R- transplant setting were associated with earlier conversion toward CC. Chronic GvHD and early chimerism were associated with better overall survival (OS), while advanced recipient age and HLA-DRB1*01 were associated with lower OS.
Polymorphonuclear myeloid-derived suppressor cells protect against hyperoxia-induced bronchopulmonary dysplasia in neonatal mice through suppression of excessive inflammatory response.
Yu B, Hong G, Li Y … +2 more , Yan X, Yu Z
Cell Immunol · 2025 Aug · PMID 40517558 · Publisher ↗
BACKGROUND: Bronchopulmonary dysplasia (BPD), which primarily affects premature infants, is characterized by impaired lung development, reduced alveolarization, and chronic inflammation, leading to long-term respiratory...
BACKGROUND: Bronchopulmonary dysplasia (BPD), which primarily affects premature infants, is characterized by impaired lung development, reduced alveolarization, and chronic inflammation, leading to long-term respiratory complications. However, clinical prevention treatment of BPD remains challenging. Because immune cells may have a role in BPD pathogenesis and prevention, we investigated whether polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) protect against hyperoxia-induced BPD in a neonatal mouse model. METHODS: Neonatal C57BL/6 mice were exposed to either normoxia (21 % oxygen) or hyperoxia (85 % oxygen) since birth. Lung development was analyzed on postnatal days 3, 7, and 14 by using histological techniques [hematoxylin and eosin (H&E) staining and radial alveolar count (RAC) measurement]. Moreover, we used flow cytometry to identify lung myeloid-derived suppressor cell (MDSC) subsets. PMN-MDSCs' therapeutic potential at key developmental stages was evaluated through adoptive transfer experiments. PMN-MDSC transplantation outcomes in the lung tissues were assessed through histological analysis, immunofluorescence staining for alveolar and vascular markers, and proinflammatory cytokine measurement. RESULTS: Hyperoxia-exposed mice exhibited considerable lung damage, including enlarged and irregular alveoli, low RACs, and decreased body weights compared with normoxic controls. Hyperoxia reduced PMN-MDSC numbers but increased monocytic MDSC numbers. PMN-MDSC transplantation preserved alveolar structure and increased alveolar and pulmonary vessel numbers. Immunofluorescence staining confirmed enhanced alveolar and vascular development. Finally, PMN-MDSCs reduced proinflammatory cytokine levels in lung tissues. CONCLUSION: PMN-MDSCs may protect against hyperoxia-induced lung injury by promoting alveolar and vascular development and reducing inflammation in neonatal mice. Further research elucidating precise mechanisms underlying the protective effects of PMN-MDSCs and their potential for clinical translation is warranted.
Gliadin amplifies the macrophage response triggered by stressed beta cells.
Jørgensen TZ, Josefsen K, Dissing SS … +3 more , Buschard K, Antvorskov JC, Larsen J
Cell Immunol · 2025 Aug · PMID 40517557 · Publisher ↗
In humans, a gluten-free diet can slow disease progression and improve clinical outcome in newly diagnosed type 1 diabetes patients. In NOD mice, the incidence of autoimmune diabetes is influenced by both beta cell activ...
In humans, a gluten-free diet can slow disease progression and improve clinical outcome in newly diagnosed type 1 diabetes patients. In NOD mice, the incidence of autoimmune diabetes is influenced by both beta cell activity and gluten. Here, we demonstrate that metabolically stressed pancreatic cell lines (MIN6, beta TC3, and alpha TC3) effectively activated macrophage RAW 264.7 cells. Gliadin further enhanced this response in MIN6 cells but had no such effect on beta TC3 or alpha TC3 cells. Additionally, gliadin directly stimulated MIN6 cells, affecting pathways related to cellular activation, stress responses, and immune regulation. These findings provide insights into the in vivo benefits of a gluten-free diet in type 1 diabetes development by highlighting the roles of cellular stress and gliadin in disease progression.
Macrophage heterogeneity in autoimmune diseases.
Li S, Zhou X, Yu S … +4 more , Liu Z, Sun M, Si Z, Zhu W
Cell Immunol · 2025 Aug · PMID 40516246 · Publisher ↗
The pathogenesis of autoimmune diseases (AIDs) is complex and their etiology remains unclear, with multiple cell types involved in the disease progression. Macrophages, as a crucial immune cell population in AIDs, play a...
The pathogenesis of autoimmune diseases (AIDs) is complex and their etiology remains unclear, with multiple cell types involved in the disease progression. Macrophages, as a crucial immune cell population in AIDs, play a pivotal role in maintaining immune homeostasis. In traditional research, macrophages are frequently oversimplified into the M1 and M2 polarized subtypes. The advent of single-cell RNA sequencing (scRNA-seq) technology has significantly advanced high-throughput research in the life sciences, enabling in-depth investigations at the cellular and molecular levels. This technology has revealed the significant heterogeneity of macrophages, further enhancing our understanding of their development, phenotypic diversity, and functional plasticity. Additionally, it provides a novel perspective for exploring the molecular mechanisms underlying various diseases. In this review, we comprehensively explore the heterogeneity of macrophages across different AIDs, and summarize potential therapeutic targets for macrophage-directed interventions, aiming to provide valuable theoretical insights and novel research directions to advance precision therapy and related studies in AIDs.
Aerobic exercise activates let-7e-5p through TP73-AS1 to inhibit the HMGB1/RAGE axis and alleviate asthma airway inflammation and remodeling.
Wang D, Zhao J, Yang C … +2 more , Qin D, Zhu D
Cell Immunol · 2025 Aug · PMID 40499319 · Publisher ↗
The rising incidence of asthma, a chronic respiratory condition, has been associated with the involvement of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in its pathogenesis. Nevertheless, there is a shortage of...
The rising incidence of asthma, a chronic respiratory condition, has been associated with the involvement of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in its pathogenesis. Nevertheless, there is a shortage of data pertaining to the impact of lncRNA TP73-AS1 and let-7e-5p on this disease. Therefore, we aimed to explore the possible effects of aerobic exercise (AE) on lncRNA TP73-AS1, let-7e-5p, inflammation, and high mobility group box 1 (HMGB1)/receptor for advanced glycation end products (RAGE) in asthma mouse models. HMGB1/RAGE was significantly upregulated in asthma mouse models using ovalbumin (OVA) stimulation. The overexpression of let-7e-5p, which was found to be significantly downregulated in asthma mouse models, appeared to inhibit EMT and might alleviate airway inflammation in asthmatic mice through the suppression of the HMGB1/RAGE pathway. Aerobic exercise was associated with reduced airway inflammation and remodeling in asthmatic mice, and appeared to suppress TP73-AS1 expression in asthma OVA-mouse models. Furthermore, TP73-AS1 may exacerbate airway inflammation and remodeling in OVA-induced asthmatic mice by downregulating let-7e-5p expression, which could activate the HMGB1/RAGE-NF-κB pathway. These findings suggest potential innovative approaches for asthma management, which warrant further validation.
"Mesenchymal stem cell-derived exosomes (MSC-exosomes) in hematology: From mechanisms to clinical breakthroughs".
Ahmad I, Hussein A, Kanabar B … +8 more , Kumar A, Ramachandran T, Shankhyan A, Karthikeyan A, Thatoi DN, Aminov Z, Soleimani Samarkhazan H, Jafari Z
Cell Immunol · 2025 Aug · PMID 40499318 · Publisher ↗
Mesenchymal stem cells (MSCs) offer promising therapy because they regulate the immune system and help repair tissues. However, challenges such as low cell survival rates, immune rejection, and ethical concerns related t...
Mesenchymal stem cells (MSCs) offer promising therapy because they regulate the immune system and help repair tissues. However, challenges such as low cell survival rates, immune rejection, and ethical concerns related to their clinical use have limited their widespread application. To overcome these limitations, MSC-derived exosomes (MSC-EXOs) have emerged as an innovative and promising cell-free therapeutic strategy. MSC-EXOs are nanosized extracellular vesicles released by MSCs that carry a diverse array of bioactive molecules, including proteins, lipids, and nucleic acids. They share many benefits with MSCs, including immune regulation, anti-inflammatory effects, and tissue repair. MSC-EXOs demonstrate therapeutic potential by modulating the tumor microenvironment, suppressing tumor growth, and enhancing the efficacy of conventional therapies. They can specifically target cells, deliver therapeutic agents, and induce apoptosis in cancer cells. Additionally, MSC-EXOs can modulate the immune response, promote hematopoietic recovery, and alleviate treatment-related side effects. While MSC-EXOs present a promising therapeutic approach, several challenges remain, including the standardization of isolation and characterization methods, understanding their mechanisms of action, and ensuring both safety and efficacy. Despite these challenges, the future of MSC-EXO-based therapies in hematology is promising. Continued research efforts are essential to unravel the intricate biology of exosomes, identify novel biomarkers, and develop innovative therapeutic strategies. By harnessing the power of MSC-EXOs, we can revolutionize the treatment of hematological diseases and improve patient outcomes.
Corrigendum to "Modular activation of macrophage-like cells by beta-2-microglobulin via mitochondria and the cGAS-STING pathway" [Cell. Immunol. 413 (2025) 104962].
Corneliussen JK, Madsen HB, Zelander NT … +2 more , Nissen MH, Desler C
Cell Immunol · 2025 Aug · PMID 40484750 · Publisher ↗
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PGC1α-mediated mitochondrial fitness promotes T cell differentiation.
Damasceno LEA, Barbosa GAC, Sparwasser T … +3 more , Cunha TM, Cunha FQ, Alves-Filho JC
Cell Immunol · 2025 Aug · PMID 40480083 · Publisher ↗
Regulatory T (T) cells play a critical role in the maintenance of immune tolerance to self-antigens and suppression of excessive immune responses. They employ a distinct metabolic profile from other CD4 T cell subsets to...
Regulatory T (T) cells play a critical role in the maintenance of immune tolerance to self-antigens and suppression of excessive immune responses. They employ a distinct metabolic profile from other CD4 T cell subsets to support their differentiation and suppressive function, which is characterized by enhanced mitochondrial metabolism. Although PGC1α is considered a master regulator of mitochondrial biogenesis and function, its role in T cell differentiation remains unclear. Herein, we demonstrated that PGC1α is highly expressed in T cells compared to other CD4 T cell populations. Using a pharmacological approach, we found that its transcriptional activation in iT cells enhanced mitochondrial fitness, characterized by increased expression of mitochondrial genes, mitochondrial mass, and metabolic activity. Moreover, PGC1α activation enhanced both mouse and human iT cell differentiation, while its inhibition reduced this process. Therefore, our findings shed light on the potential role of PGC1α as a pharmacological target when manipulating T cells as a therapeutic strategy.
Fibrinogen regulates microglial function through the JAK2/STAT3 signaling pathway.
Li X, Song X, Yi F … +1 more , Hou H
Cell Immunol · 2025 Aug · PMID 40472614 · Publisher ↗
BACKGROUND: Neuroinflammation, a defining feature of numerous neurological disorders, arises predominantly from activating immune cells such as microglia, which play a critical role in maintaining homeostasis within the...
BACKGROUND: Neuroinflammation, a defining feature of numerous neurological disorders, arises predominantly from activating immune cells such as microglia, which play a critical role in maintaining homeostasis within the central nervous system. Microglial activation and polarization exhibit a dual nature, mediating both neuroprotective and neurotoxic effects. Fibrinogen, as a potent pro-inflammatory mediator, interacts with microglia and is implicated in the progression of various neurological conditions. This study investigates the effects of fibrinogen and the exogenous STAT3 inhibitor cryptotanshinone on primary microglial function. METHODS: Primary microglial cells were isolated from neonatal C57BL/6 mice and subsequently treated with fibrinogen and the STAT3 inhibitor cryptotanshinone. Inflammatory marker expression was quantified by quantitative polymerase chain reaction, while protein levels of JAK2 and STAT3 were determined using immunofluorescence and Western blot analysis. RESULTS: Fibrinogen exposure upregulated STAT3 and JAK2 phosphorylation in primary microglial cells. Cryptotanshinone treatment effectively attenuated STAT3 phosphorylation while concurrently downregulating JAK2 activation. Furthermore, fibrinogen significantly enhanced the release of pro-inflammatory cytokines, such as IL-6 and IL-1β, while the transcription levels of TGF-β remained unchanged. CONCLUSIONS: This study demonstrates that fibrinogen stimulates the production of pro-inflammatory cytokines in primary microglial cells by activating the JAK2/STAT3 signaling pathway. These findings provide mechanistic insights into fibrinogen-induced neuroinflammation and suggest potential therapeutic targets for neurological diseases.
Retraction notice to "Protective efficacy of a plasmid DNA vaccine against transgene-specific tumors by Th1 cellular immune responses after intradermal injection" [Cell. Immunol. 329 (2018) 17-26].
Son HY, Apostolopoulos V, Chung JK … +2 more , Kim CW, Park JU
Cell Immunol · 2025 Jul · PMID 40447479 · Publisher ↗
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Integrated proteomics and phosphoproteomics profiling dynamic signaling networks underlying two distinct types of macrophage activation.
Wu L, Xu H, Zhang X … +10 more , Zhang M, Xu Y, Zhang Q, Tao H, Dong C, Zhang X, Zhou M, Yang J, Lin C, Song Q
Cell Immunol · 2025 Jul · PMID 40398355 · Publisher ↗
Macrophages play a crucial role in antimicrobial host defense and those with differential maturation/differentiation status differ in inflammatory responses. Herein, GM-CSF and M-CSF primed mouse bone marrow derived macr...
Macrophages play a crucial role in antimicrobial host defense and those with differential maturation/differentiation status differ in inflammatory responses. Herein, GM-CSF and M-CSF primed mouse bone marrow derived macrophages (GM-BMDMs, GM and M-BMDMs, M), the well-established macrophage models in vitro, were utilized and their dynamic signaling changes in response to gram-negative bacteria component LPS treatment were analyzed using both 4D label-free proteomics and phosphoproteomics. Protein changes maintained relatively constant within or across GM and M macrophages post LPS challenge while phospho-protein exhibited more diverse and transient changes. Early induction of phospho-mediated GTPase activities, mRNA processing, and protein-mediated metabolic changes like oxidative phosphorylation (OXPHOS)/mitochondria function was identified at 1 h and maintained until 6 h post LPS treatment in GM and M while canonical TLR mediated MyD88-dependent and -independent pathways were activated at 3 and 6 h, individually at protein levels. Classical and novel phospho-sites for MyD88 and TRIF signaling pathways were also detected by phosphoproteomics. Comprehensively, the integrated protein and phospho-protein trend analysis was conducted and the core protein-phospho-protein network for the early phase actin reorganization, phagocytosis, and TLR signaling in both GM and M were presented. Taken together, these data described differences and similarities between these two types of macrophages in terms of their inflammatory responses to LPS.
METTL3 facilitates osteoblast differentiation and bone regeneration via m6A-dependent maturation of pri-miR-324-5p.
Xiao J, Xu Z, Deng Z … +2 more , Xie J, Qiu Y
Cell Immunol · 2025 Jul · PMID 40398354 · Publisher ↗
BACKGROUND: Osteoblast differentiation is essential for fracture healing and bone regeneration. miR-324-5p has been implicated in osteoporosis, but its precise role in osteogenic differentiation remains unclear. We inves...
BACKGROUND: Osteoblast differentiation is essential for fracture healing and bone regeneration. miR-324-5p has been implicated in osteoporosis, but its precise role in osteogenic differentiation remains unclear. We investigated the function and regulatory mechanisms of miR-324-5p in bone marrow mesenchymal stem cells (BMSCs). METHODS: RT-qPCR was used to assess miR-324-5p expression during osteogenic differentiation of BMSCs. ALP, Alizarin Red S (ARS), Oil Red O, and TRAP staining were performed to evaluate osteoblast, adipocyte, and osteoclast differentiation. Rat femoral fracture and calvarial bone defect models were established to assess in vivo bone regeneration. Methylated RNA immunoprecipitation (MeRIP) and luciferase reporter assays were used to investigate METTL3-mediated m6A modification of pri-miR-324-5p and its regulation of ELAVL1. RESULTS: miR-324-5p expression increased during osteogenic differentiation, and ALP and ARS staining confirmed enhanced osteoblast activity and mineralization following miR-324-5p overexpression. Meanwhile, Oil Red O staining showed reduced adipogenic differentiation, and TRAP staining demonstrated suppressed osteoclast formation. In vivo, miR-324-5p promoted bone healing, bone mass, and bone regeneration. Mechanistically, METTL3-mediated m6A modification facilitated pri-miR-324-5p maturation, positively regulating its expression. Additionally, miR-324-5p directly targeted ELAVL1, and ELAVL1 overexpression reversed the osteogenic effects of miR-324-5p. CONCLUSION: The METTL3/miR-324-5p/ELAVL1 axis plays a crucial role in osteogenic differentiation and bone regeneration, providing new insights into m6A modification-driven osteogenesis.
Zinc finger protein 217 contributes to natural killer cell dysfunction in murine colorectal cancer.
Yu Y, Yang H, Wang H … +1 more , Xiao F
Cell Immunol · 2025 Jul · PMID 40381549 · Publisher ↗
Immune cells play active roles in the surveillance and control of colorectal cancer (CRC) progression. Natural killer (NK) cells are powerful anti-tumor effector cells but their regulatory mechanisms in the CRC tissues h...
Immune cells play active roles in the surveillance and control of colorectal cancer (CRC) progression. Natural killer (NK) cells are powerful anti-tumor effector cells but their regulatory mechanisms in the CRC tissues have not been thoroughly elucidated. In this research using a murine inflammatory colorectal cancer model, we characterized the phenotype and function of NK cells. We found signs of NK cell dysfunction in CRC tissues, including up-regulation of exhaustion markers, down-regulation of activating receptors, deficiencies in degranulation and cytokine expression, and weak cytolytic effect. Interestingly, zinc finger protein 217 (ZNF217), a transcription repressor, was significantly up-regulated in CRC-associated NK cells. In vitro assays revealed that ZNF217 knockdown promoted NK cell cytolytic activity, implying that ZNF217 is an inhibitory factor of NK cell function. Adoptive transfer assays indicated that ZNF217 knockdown also resulted in enhancement of NK cell function in vivo and subsequently suppressed CRC development. Furthermore, hypoxia rather than exhaustion up-regulated ZNF217 expression in NK cells. ZNF217 knockdown promoted NK cell resistance to hypoxia-mediated NK cell dysfunction. Therefore, we discovered a novel regulatory factor of NK cell dysfunction during CRC development.
Investigating the effect of neuro-immune communication on immune responses in health and disease: Exploring immunological disorders.
Hesampour F, Bernstein CN, Ghia JE
Cell Immunol · 2025 Jul · PMID 40378510 · Publisher ↗
Recent recognition of the intricate nervous-immune system interplay has prompted research into the specific cellular components involved in these interactions. Emerging evidence suggests that immune and neural cells coll...
Recent recognition of the intricate nervous-immune system interplay has prompted research into the specific cellular components involved in these interactions. Emerging evidence suggests that immune and neural cells collaborate within distinct units and act in concert to regulate tissue function and provide protection. These specialized neuro-immune cell units have been identified in diverse body tissues, ranging from lymphoid organs to the bone marrow and mucosal barriers. Their significance has become increasingly apparent as they are recognized as pivotal regulators influencing a broad spectrum of physiological and pathological processes. This recognition extends to critical roles in hematopoiesis, organ function, inflammatory responses, and intricate tissue repair processes. This review explores the bidirectional communication between the nervous and immune systems. The focus is on understanding the profound impact of this communication on immune cells within key anatomical sites, such as the bone marrow, gastrointestinal tract, and lymphoid organs. By examining these interactions, this review aims to shed light on how this intricate network operates under normal and pathological conditions, offering insights into the mechanisms underlying health and disease.
Apelin-13 enhances neurofunctional recovery and suppresses neuroinflammation via the SIRT1/NF-κB axis in ischemic stroke.
Peng Z, Ru D, Leng G … +3 more , Peng J, Zhang M, Cai B
Cell Immunol · 2025 Jul · PMID 40378509 · Publisher ↗
BACKGROUND: 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 neur...
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Progress of exosomes in regulating tumor metastasis by remodeling the pre-metastatic immune microenvironment.
Xiang J, Yao L, Wang S … +2 more , Zhao L, Yu J
Cell Immunol · 2025 Jul · PMID 40367831 · Publisher ↗
Exosomes play an important role in the metastatic microenvironment, acting as a transmission belt that facilitates intercellular communication. By delivering proteins, nucleic acids, and other substances in the exosomes,...
Exosomes play an important role in the metastatic microenvironment, acting as a transmission belt that facilitates intercellular communication. By delivering proteins, nucleic acids, and other substances in the exosomes, they can change the function of the receptor target cells, change the microenvironment of the metastatic site, and promote the colonization of the tumor cells, thus promoting cancer metastasis. The interaction between tumor cells and the surrounding microenvironment is complex, with exosomes serving as key facilitators of crosstalk between the primary tumor microenvironment and the pre-metastasis microenvironment. Despite many current studies to explore exosomes, we still do not have a detailed understanding of the role and mechanism of exosomes in the pre-metastatic immune microenvironment, and there are many challenges in the clinical application of exosomes. In this paper, we summarize the role of exosomes in regulating the pre-metastatic immune microenvironment and its mechanism, focusing on how exosomes regulate the function of immune cells in the pre-metastatic microenvironment to promote tumor metastasis. In addition, the potential application of exosomes in tumor immunotherapy and strategies for targeting exosomes are discussed. This will contribute to the immunotherapy of cancer metastasis and promote the clinical application of exosomes.
Characterization of lysate from NK-92 cells and its potential use as an immunotherapeutic modality.
Chinnapen H, Boissel L, Fleenor C … +6 more , Bickett T, Guo Z, Godbole V, Saxena M, Soon-Shiong P, Klingemann H
Cell Immunol · 2025 Jul · PMID 40347562 · Publisher ↗
Lysates from human cells represent biofluids that are used in the biotechnology field for a number of reasons such as biomarker identification and antibody detection. Lysate from human blood platelets is widely used in t...
Lysates from human cells represent biofluids that are used in the biotechnology field for a number of reasons such as biomarker identification and antibody detection. Lysate from human blood platelets is widely used in the clinical setting to control bleeding. We hypothesized that the lysate from the cytotoxic natural killer cell line NK-92® should contain perforin and proteolytic enzymes in addition to immunomodulatory cytokines, all of which have biological relevance and could be used for local treatment of cancer lesions. Here lysate from NK-92 (aNK™) cells, and its erIL-2 engineered variant haNK™ was obtained by repeat freeze/thawing. Immunoblot, ELISA and cytokine immunoassay analysis confirmed the presence of perforin and the full spectrum of granzymes, as well as of various chemokines and cytokines known to be expressed in NK-92 cells. Lysate from haNK cells displayed cytotoxic and anti-proliferative activity against human and canine cancer cell lines after only a 15-min exposure in vitro. Importantly, under the same conditions the lysate did not affect primary cells. Intra-tumor injection of haNK lysate into intradermal tumors of immunocompetent C57BL/6 mice provided tumor control in 40 % of treated animals. When re-challenged with the same tumor line several weeks after primary tumor clearance, no growth occurred indicating that intra-tumor administration of haNK lysate can generate a vaccine-like effect.
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