Cellular Immunology[JOURNAL]
Sun
200 papers
Modular activation of macrophage-like cells by beta-2-microglobulin via mitochondria and the cGAS-STING pathway.
Corneliussen JK, Madsen HB, Zelander NT … +2 more , Nissen MH, Desler C
Cell Immunol · 2025 Jul · PMID 40345004 · Publisher ↗
Beta-2-microglobulin (β2m) is a component of the major histocompatibility complex class I. β2m is released into cellular fluids in response to various stimuli, including pro-inflammatory cytokines. Elevated β2m levels ha...
Beta-2-microglobulin (β2m) is a component of the major histocompatibility complex class I. β2m is released into cellular fluids in response to various stimuli, including pro-inflammatory cytokines. Elevated β2m levels have been found associated with autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and Crohn's disease, as well as in various hematological cancers and viral infections. Despite an established correlation between immune activation of especially monocytes and macrophages, and circulating β2m levels, the causative relationship remains unclear. Here, we investigate the effects of exogenous β2m and a complement C1s cleaved form, dK58β2m, on two murine macrophage-like cell lines J774 and RAW. We demonstrate that β2m, and to a greater extent dK58β2m, can affect mitochondrial activity. Furthermore, the presence of IFN-γ amplifies the effect, causing altered bioenergetics, and increased production of mitochondrial reactive oxygen species and nitric oxide. In addition, we found activation of the cGAS-STING pathway by β2m and dK58β2m in the presence of IFN-γ. Only dK58β2m in combination with IFN-γ caused apoptosis and cell death. Our findings highlight the modular nature of a β2m-induced macrophage response, potentiated by dK58β2m and IFN-γ, and provide information on the underlying mechanisms responsible for the immune activation properties of β2m.
The NLRP3 Inflammasome in inflammatory diseases: Cellular dynamics and role in granuloma formation.
de Oliveira IM, Chaves MM
Cell Immunol · 2025 · PMID 40339528 · Publisher ↗
The innate immune system recognizes pathogen-associated molecular patterns (PAMPs) and damage associated molecular patterns (DAMPs) through pattern recognition receptors (PRRs). Inflammasomes, cytoplasmic protein complex...
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.
miRNA-186-5p modulates placental inflammation via Inflammasome activation in gestational diabetes mellitus.
Megha B, Milan KL, Anuradha M … +1 more , Ramkumar KM
Cell Immunol · 2025 · PMID 40315793 · Publisher ↗
Inflammasomes are multiprotein complexes that initiate inflammatory responses by activating pro-inflammatory cytokines, playing a crucial role in innate immunity. However, their dysregulation can lead to excessive inflam...
Inflammasomes are multiprotein complexes that initiate inflammatory responses by activating pro-inflammatory cytokines, playing a crucial role in innate immunity. However, their dysregulation can lead to excessive inflammation, particularly in conditions like gestational diabetes mellitus (GDM), where placental inflammation may adversely affect fetal development and increase the risk of complications. NEK7 (NIMA-related kinase 7) has been identified as a key mediator in inflammasome activation, facilitating the complex assembly and amplifying inflammatory responses. This study aims to investigate the regulatory role of miRNA in inflammasome-mediated placental inflammation through its interaction with NEK7 in the pathophysiology of GDM. In-silico analysis identified that NEK7 is a direct target of miR-186-5p, while PCR analysis demonstrated a significant loss of miR-186-5p expression in GDM placental tissues. Further, the expressions of NEK7, NLRP1, NLRP3, Caspase 1 along with the inflammatory cytokines were significantly elevated in GDM placenta. Furthermore, the correlation analysis demonstrated a significant negative correlation between miR-186-5p and NEK7 expression levels, suggesting that the loss of miR-186-5p may contribute to inflammasome mediated placental inflammation in GDM. Additionally, the overexpression of miR-186-5p decreased the high glucose induced inflammation and the expressions of NEK7, NLRP1 and NLRP3 in BeWo cell line. Therefore, this study concludes that miR-186-5p may attenuate the activation of inflammasome and regulate inflammation via NEK7 in the progression of GDM. Understanding these molecular mechanisms offers valuable insights into potential therapeutic targets aimed at improving pregnancy outcomes in GDM.
Potential therapeutic strategies targeting efferocytosis for inflammation resolution and tissue repair in inflammatory bowel disease.
Li C, Liu W, Fu A … +2 more , Yang H, Yi G
Cell Immunol · 2025 · PMID 40315792 · Publisher ↗
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. Infla...
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.
Transfer of bone marrow niche-residential regulatory T cells ameliorates experimental colitis.
Meng C, Sato T, Ueda R … +3 more , Kim J, Longhi MS, Fujisaki J
Cell Immunol · 2025 · PMID 40306133 · Full text
BACKGROUND: 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....
BACKGROUND: 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, 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 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. Yet, the treatment effects of transferred BM niche Tregs in non-BM disease settings remain unknown. OBJECTIVES: 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. STUDY DESIGN: 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. RESULTS: The transfer of as few as 1.5 × 10 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. CONCLUSION: 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.
The real-world impact of corticosteroid-associated adverse events in myasthenia gravis: A patient-reported survey analysis.
Yan J, Choi K, Fu P … +6 more , Yang M, Lin J, Gui M, Li Y, Bu B, Li Z
Cell Immunol · 2025 · PMID 40306132 · Publisher ↗
BACKGROUND: Corticosteroids are crucial for managing acute exacerbation symptoms and preventing relapses in myasthenia gravis (MG) patients. METHODS: Between April 15-30, 2024, 2368 online self - report questionnaires we...
BACKGROUND: Corticosteroids are crucial for managing acute exacerbation symptoms and preventing relapses in myasthenia gravis (MG) patients. METHODS: Between April 15-30, 2024, 2368 online self - report questionnaires were distributed. Eventually, 444 MG patients who had received corticosteroid therapy completed the survey. RESULTS: 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. CONCLUSION: 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.
Lupeol mitigates spinal cord injury by modulating microglial M1/M2 polarization via Na/K-ATPase-mediated mitophagy.
Liu R, Yue Z, Dong J … +3 more , Zhang C, Guo C, Wang X
Cell Immunol · 2025 · PMID 40279871 · Publisher ↗
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 specif...
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.
Aged mice-derived bronchial epithelial cells regulate Th17 cell differentiation in asthma via the MBD2-sICOSL axis.
Chen Z, Shang Y, Yuan Y … +4 more , Ji X, Gong S, Zeng Q, Xiang X
Cell Immunol · 2025 · PMID 40252480 · Publisher ↗
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...
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.
Hyperoside suppresses NSCLC progression by inducing ATG13-mediated autophagy and apoptosis.
Jin M, Lou Y, Wang X … +3 more , Lv J, Wu Y, Huang G
Cell Immunol · 2025 · PMID 40250077 · Publisher ↗
BACKGROUND: Lung cancer is a leading cause for cancer-related mortality across the globe. In the last decade, significant advancements have been made in the research of non-small cell lung cancer (NSCLC). However, new bi...
BACKGROUND: Lung cancer is a leading cause for cancer-related mortality across the globe. In the last decade, significant advancements have been made in the research of non-small cell lung cancer (NSCLC). However, new biotherapeutic drugs urgently need to be developed. This study investigated the regulating effect of hyperoside on NSCLC progression. METHODS: The colony formation assay and Cell Counting Kit-8 were used to detect cell proliferation. The Transwell assay was used to monitor cell migration. NSCLC growth in vivo was examined using a subcutaneous xenograft model. Proteomics, immunohistochemistry, and immunofluorescence analyses were used to detect anticancer regulatory mechanisms. RESULTS: The results showed that hyperoside treatment inhibited cell migration, proliferation, and tumor growth in NSCLC in vivo and in vitro. Also, hyperoside treatment promoted apoptosis and cell cycle S-phase arrest. Proteomics, immunohistochemistry, and immunofluorescence detection also showed that hyperoside treatment promoted autophagy-related protein 13 (ATG13)-mediated autophagy, which further increased NSCLC apoptosis. CONCLUSION: In summary, the findings illustrated that hyperoside treatment suppressed NSCLC progression by promotingATG13 expression and enhancing autophagy activation, finally promoting autophagy and apoptosis.
Role of CD44CCR2CD64monocyte-derived macrophage in chronic rhinosinusitis with nasal polyps.
Zhang Y, Yang M, Li Y … +8 more , Wang Z, Zhang S, Zhao L, Liu Y, Li X, Wang X, Lan F, Zhang L
Cell Immunol · 2025 · PMID 40239553 · Publisher ↗
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 rem...
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 ex vivo polarized MDMs. By using appropriate substitutes for tissue MDMs, we investigated the function of MDMs. MDM1 (linCD44CD64) and MDM3 (linCD44CCR2CD64) 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. Ex vivo 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 Staphylococcus aureus 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.
Novel and effective tandem CD38 and CD19 targeting CAR-T cells inhibit hematological tumor immune escape.
Liu X, Feng Y, Song Z … +4 more , Liu J, Luo Z, Yu G, Wang J
Cell Immunol · 2025 · PMID 40239552 · Publisher ↗
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 viabl...
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. In vitro 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. In vivo 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.
MAPK14 drives Ferroptosis and immune dysfunction in pediatric Sepsis-induced acute lung injury.
Zhang N, Fan Y, Chen J … +2 more , Gu J, Yan X
Cell Immunol · 2025 · PMID 40209319 · Publisher ↗
OBJECTIVE: Sepsis-induced acute lung injury (ALI) is driven by inflammation, oxidative stress, and immune suppression. MAPK14 (p38α) plays a role in ferroptosis and immune regulation, but its specific function in pediatr...
OBJECTIVE: Sepsis-induced acute lung injury (ALI) is driven by inflammation, oxidative stress, and immune suppression. MAPK14 (p38α) plays a role in ferroptosis and immune regulation, but its specific function in pediatric sepsis remains unclear. Therefore, our study aimed to explore the role and underlying mechanism of MAPK14 in pediatric sepsis. METHODS: Bioinformatics analysis of GSE26440 and FerrDb identified ferroptosis-related genes in pediatric sepsis. STRING database was used to predict the proteins associated with MAPK14. MAPK14 expression in whole blood samples, LPS-treated MLE-12 cells, and a CLP mouse model was detected by qRT-PCR and western blot. Ferroptosis was assessed by measuring MDA, GSH, and Fe levels, while ROS accumulation was analyzed using DCFH-DA staining and DHE staining. A cycloheximide (CHX) assay was performed to assess TTP53 protein stability. MPO immunohistochemistry and PD-L1 immunofluorescence assessed neutrophil infiltration, and flow cytometry evaluated neutrophil apoptosis. RESULTS: Bioinformatics analysis of GSE26440 and FerrDb identified MAPK14 as a ferroptosis-related gene in pediatric sepsis. MAPK14 expression was upregulated in sepsis patient samples, LPS-treated MLE-12 cells and CLP mouse lung tissues. Overexpression of MAPK14 led to increased MDA and Fe levels, reduced GSH, and elevated ROS fluorescence intensity, confirming its role in promoting ferroptosis. Mechanistically, MAPK14 upregulated TTP53, which in turn suppressed SLC7A11 and GPX4, further driving ferroptosis. MAPK14 overexpression stabilized TTP53 and enhanced its activity. Additionally, MAPK14 enhanced MPO and PD-L1 expression to promote neutrophil infiltration and immune suppression. Additionally, MAPK14 overexpression inhibited neutrophil apoptosis, promoted neutrophil infiltration and enhanced immune suppression. CONCLUSION: MAPK14 drives ferroptosis via the TTP53/SLC7A11/GPX4 pathway and exacerbates immune suppression by promoting neutrophil infiltration.
A new chimeric protein composed by T-cell epitopes from peroxidoxin and pyridoxal kinase proteins is protective against visceral leishmaniasis.
Lage DP, Vale DL, Silva MGP … +18 more , Martins VT, Gonçalves AAM, Silva KA, Moreira GJL, Olegário RD, Rizzatti FC, Freitas CS, Pimenta BL, Falcão KOM, Dias SSG, Oliveira-da-Silva JA, Câmara RSB, Pereira IAG, Chávez-Fumagalli MA, Roatt BM, Machado-de-Ávila RA, Galdino AS, Coelho EAF
Cell Immunol · 2025 · PMID 40198961 · Publisher ↗
Visceral leishmaniasis (VL) is a neglected tropical disease caused by intracellular protozoan parasites, and which present high incidence in populations in the world. The diagnosis is difficult to be performed, and treat...
Visceral leishmaniasis (VL) is a neglected tropical disease caused by intracellular protozoan parasites, and which present high incidence in populations in the world. The diagnosis is difficult to be performed, and treatment is toxic and/or presents high cost. In this context, prophylactic vaccination could help as an effective control measure against the disease. In this study, a new chimeric protein (LAV) was constructed with immunogenic T-cell epitopes from two immunogenic Leishmania proteins, and it was evaluated to protects BALB/c mice against Leishmania infantum infection. For this, animals were vaccinated with rLAV associated with micelles (Mic) or monophosphoryl lipid A (MPLA) as adjuvants; while the others received saline, rLAV, Mic or MPLA as controls. Results showed that the rLAV/Mic and rLAV/MPLA combinations induced higher cell proliferation indexes in stimulated cell cultures after infection, as well as the development of a polarized Th1-type cellular and humoral response before and after infection, which was based on the production of IFN-γ, IL-12, TNF-α, nitrite, and IgG2a isotype antibodies. In addition, both CD4 and CD8 T-cell subtypes were important for the IFN- secretion in both groups, as compared to the others. Control groups mice produced significantly higher levels of IL-4, IL-10 and anti-parasite IgG1 antibodies, suggesting the occurrence of a Th2-type immune profile in these unprotected animals. The parasite load was found to be significantly lower in mice vaccinated with rLAV/MPLA or rLAV/Mic, as compared to the others, by using a limiting dilution assay and qPCR. In conclusion, data suggest that rLAV plus adjuvant could be considered as a vaccine candidate in future studies to protect against VL.
Immunology of familial chorea-acanthocytosis with presenting generalized tonic-clonic seizure: Blood cell study for early diagnosis and management.
Salem A, Omidvar N
Cell Immunol · 2025 · PMID 40184858 · Publisher ↗
A male, who involved familial chorea-acanthocytosis (ChAc), was introduced to provide direction for early diagnosis and management. The admitted patient was found to have the significant episode with generalized tonic-cl...
A male, who involved familial chorea-acanthocytosis (ChAc), was introduced to provide direction for early diagnosis and management. The admitted patient was found to have the significant episode with generalized tonic-clonic seizure, gradually progressive abnormal movements, and generalized weakness. According to the peripheral blood smears, the acanthocytosis was diagnosed primarily. The neuroimaging observation revealed atrophied head of caudate nuclei and dilation of anterior horn in the lateral ventricles. For the early diagnosis and prevention of syndrome complications, neuroacanthocytosis should be considered in the differential diagnosis of patients presenting with generalized tonic-clonic seizure, peripheral neuropathy, and behavioral disorder associated with movement complications.
Immunity in children: How does it begin?
Fillatreau S
Cell Immunol · 2025 · PMID 40157806 · Publisher ↗
Abstract loading — click title to view on PubMed.
METTL3 promotes infantile pneumonia-induced lung injury by the m6A-TBL1XR1-ACSL1 axis.
Song F, Guo F, Su B … +4 more , Niu N, Sun L, Yan M, Liu M
Cell Immunol · 2025 · PMID 40117788 · Publisher ↗
BACKGROUND: Methyltransferase-like 3 (METTL3) is the catalytic subunit of methyltransferase complex that catalyzes mRNA methylation and has been identified to be involved in lipopolysaccharide (LPS)-induced lung cell inj...
BACKGROUND: Methyltransferase-like 3 (METTL3) is the catalytic subunit of methyltransferase complex that catalyzes mRNA methylation and has been identified to be involved in lipopolysaccharide (LPS)-induced lung cell injury. In this study, we investigated whether METTL3 is involved in the progression of infantile pneumonia (IP)-induced lung injury and its underlying mechanism. METHODS: WI-38 cells were exposed to LPS to induce in vitro proliferation, inflammation, apoptosis, and ferroptosis. The mRNA and protein levels of METTL3, TBL1XR1, IGF2BP1/2/3, and ACSL1 were measured by qRT-PCR and western blotting, respectively. The N6-methyladenosine (m6A) modification was analyzed using a methylated RNA immunoprecipitation assay. Protein interactions were determined using a Co-IP assay. LPS-induced pneumonia in mice was used for the in vivo analysis. RESULTS: METTL3 was highly expressed in IP and LPS-induced WI-38 cells. Knockdown of METTL3 reversed LPS-induced apoptosis, inflammation, and ferroptosis in vitro and in vivo and improved LPS-induced lung injury and collagen deposition in lung tissues of IP mice. Mechanistically, METTL3 induces TBL1XR1 m6A modifications and stabilizes its expression in an m6A-IGF2BP1-dependent manner. Functionally, the protective effects mediated by METTL3 silencing in LPS-treated WI-38 cells were reversed by TBL1XR1 overexpression. In addition, TBL1XR1 interacts with ACSL1, and METTL3 regulates ACSL1 expression via TBL1XR1. Further functional analysis showed that TBL1XR1 deficiency suppressed LPS-induced apoptosis, inflammation, and ferroptosis, which were abolished by ACSL1 up-regulation. CONCLUSION: METTL3 stabilized TBL1XR1 expression through IGF2BP1-m6A methylation, promoting LPS-induced IP lung injury by upregulating ACSL1 expression.
Dexmedetomidine modulates peritoneal macrophage to attenuate lipopolysaccharide-induced inflammation.
Wang T, Pan R, Wen J … +1 more , Ma X
Cell Immunol · 2025 · PMID 40088848 · Publisher ↗
PURPOSE: To investigate how Dexmedetomidine (Dex) modulates the function of peritoneal macrophages (PMs) to reduce lipopolysaccharide (LPS)-induced inflammation. METHODS: The anti-inflammatory effect of Dex on LPS-stimul...
PURPOSE: To investigate how Dexmedetomidine (Dex) modulates the function of peritoneal macrophages (PMs) to reduce lipopolysaccharide (LPS)-induced inflammation. METHODS: The anti-inflammatory effect of Dex on LPS-stimulated PMs was assessed by examining its impact on their proliferation, phagocytosis, and polarization. Proliferation and phagocytic activity were measured using CCK-8 and Neutral Red staining assays, respectively. The levels of inflammatory mediators were quantified using ELISA. Additionally, macrophage polarization was evaluated via ELISA, flow cytometry, and Western blot analysis to identify shifts in macrophage phenotypes. RESULTS: Dex increased the proliferation and phagocytic capabilities of PMs, thereby mitigating LPS-induced inflammation. It suppressed pro-inflammatory mediators, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and high mobility group box 1 (HMGB1), while increasing levels of the anti-inflammatory cytokine interleukin-10 (IL-10). Furthermore, Dex promoted M2-type macrophage polarization, characterized by increased expression of IL-10, CD206, Arg-1, and CD11c. This effect was mediated through the JAK1/STAT6 signaling pathway, promoting M2 polarization, which was attenuated when JAK1 and STAT6 expression were downregulated. CONCLUSION: Dex reduces LPS-induced inflammation in part by enhancing the proliferation, phagocytosis, and M2 polarization of PMs, with a key role for the JAK1/STAT6 pathway in promoting anti-inflammatory responses during sepsis.
USP14 inhibits sensitization-mediated degradation of KDM4D to epigenetically regulate dendritic cell tolerogenic capacity and mitigates airway allergy.
Zhang A, Zhang H, Liu L … +8 more , Zhang H, Mo L, Zhang W, Harith HH, Cheng L, Lv J, Tham CL, Yang P
Cell Immunol · 2025 · PMID 40088847 · Publisher ↗
Numerous immune disorders are caused by the dysfunction of dendritic cells (DC). The mechanism has not been fully comprehended yet. This research is designed to regulate the epigenetic status of lysine-specific demethyla...
Numerous immune disorders are caused by the dysfunction of dendritic cells (DC). The mechanism has not been fully comprehended yet. This research is designed to regulate the epigenetic status of lysine-specific demethylase 4D (KDM4D) to enhance DC's immune tolerogenic capacity. In this study, an airway allergy (AA) mouse model was established with dust mite extracts (DME) as the specific antigen. A mouse strain carrying Kdm4d-deficient DCs was employed in the experiments to assess the role of KDM4D in modulating DC's immune tolerogenic functions. The results showed that mice carrying Kdm4d-deficient DCs (KO mice) showed spontaneous Th2 polarization in the airways. Reduced quantities of KDM4D were detected in airway naive DCs (nDCs) of AA mice. The parameters of AA response had a negative correlation with the quantity of KDM4D. The immune tolerogenic capacity of airway nDCs was impaired in KO mice as well as in AA mice. The Il10 promoter was found to be hypermethylated in airway nDCs of AA mice and KO mice. The low quantity of deubiquitinating enzyme 14 (USP14) was related to the high level of hyper ubiquitination observed in KDM4D in the Il10 promoter locus of airway nDCs of AA mice. Exposure to recombinant USP14 increased the quantity of KDM4D in nDCs, restoring the immune tolerogenic capacity of nDCs in AA mice. In conclusion, dysfunctional tolerogenicity is caused by low levels of KDM4D in airway nDCs from AA mice. USP14 restores the tolerogenic capacity of nDCs in AA mice and mitigates experimental AA.
Divergent impact of endotoxin priming and endotoxin tolerance on macrophage responses to cancer cells.
Roy K, Jędrzejewski T, Sobocińska J … +5 more , Spisz P, Maciejewski B, Hövelmeyer N, Passeri B, Wrotek S
Cell Immunol · 2025 · PMID 40054049 · Publisher ↗
Endotoxin tolerance (ET) is an adaptive phenomenon that arises from the repeated exposure of immune cells, such as macrophages, to endotoxins like lipopolysaccharide (LPS). Initially, when macrophages are activated by LP...
Endotoxin tolerance (ET) is an adaptive phenomenon that arises from the repeated exposure of immune cells, such as macrophages, to endotoxins like lipopolysaccharide (LPS). Initially, when macrophages are activated by LPS, they produce inflammatory mediators that drive the primary immune response. However, this response is significantly diminished during the establishment of ET, creating an immunosuppressive environment. This environment can facilitate the development and progression of malignant conditions, including cancer. Our research focused on the interactions between immune cells and the tumor microenvironment under ET conditions. Through comprehensive in vivo and in vitro studies employing various research techniques, we have demonstrated that interactions between endotoxin-tolerant macrophages (Mo) and cancer cells contribute to a pro-tumorigenic condition. Notably, we observed that Mo adapt a pro-tumorigenic, immunosuppressive M2 phenotype (CD163 expression). These macrophages involves distinct metabolic pathways, not depending solely on glycolysis and oxidative phosphorylation. Furthermore, our in vivo findings revealed macrophage infiltration within tumors under both ET and non-ET conditions, highlighting the suppressed immune landscape in the presence of ET. These findings suggest that ET plays a pivotal role in shaping tumor-associated immune responses and that targeting ET pathways could offer a novel and promising therapeutic approach for cancer treatment.
Nebulized mesenchymal stem cell-derived exosomes attenuate airway inflammation in a rat model of chronic obstructive pulmonary disease.
Wang M, Hao Y, He W … +3 more , Jia H, Zhong Z, Xia S
Cell Immunol · 2025 · PMID 40020434 · Publisher ↗
Chronic Obstructive Pulmonary Disease (COPD) is one of the leading causes of death worldwide, and current treatments fail to significantly halt its progression. Exosomes derived from mesenchymal stem cells (MSCs-Exos) ha...
Chronic Obstructive Pulmonary Disease (COPD) is one of the leading causes of death worldwide, and current treatments fail to significantly halt its progression. Exosomes derived from mesenchymal stem cells (MSCs-Exos) have demonstrated promising potential in treating COPD due to their anti-inflammatory and regenerative biological properties. In this study, we investigated the potential anti-inflammatory effects of bone marrow mesenchymal stem cell-derived exosomes (BMSCs-Exos) in a COPD rat model and the possible mechanisms by which they inhibit airway remodeling, as well as identifying the optimal dosage and administration route. Our results show that nebulized BMSC-Exos significantly improve lung function in COPD rats while reducing pulmonary inflammatory infiltration, bronchial mucus secretion, and collagen deposition. Moreover, BMSC-Exos treatment notably decreased the expression of pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1β, and the pro-fibrotic factor TGF-β1 in serum, bronchoalveolar lavage fluid (BALF), and lung tissue. The most pronounced therapeutic effect was observed at a low dose of exosomes. Furthermore, quantitative real-time PCR and immunohistochemical analyses revealed that nebulized BMSC-Exos significantly inhibited airway remodeling and epithelial-mesenchymal transition (EMT) by suppressing the Wnt/β-catenin signaling pathway. In conclusion, these findings indicate that nebulized BMSC-Exos offer a noninvasive therapeutic strategy for COPD by mitigating lung inflammation and airway remodeling through the suppression of abnormal Wnt/β-catenin pathway activation induced by cigarette smoke (CS) and lipopolysaccharide (LPS) in rats.
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