Cellular Immunology[JOURNAL]
Sun
200 papers
In vitro ovarian tumor-conditioned CD163+ human macrophages retain phagocytic response to CD47 blockade.
Antonsen KW, Jensen AG, Sorensen BS … +3 more , Etzerodt A, Moestrup SK, Møller HJ
Cell Immunol · 2025 · PMID 39985839 · Publisher ↗
INTRODUCTION: CD163-expressing macrophages are abundant in ovarian cancer where they accelerate tumor growth and metastasis. CD47 blockade is a novel immunotherapy aiming to activate macrophage phagocytosis of tumor cell...
INTRODUCTION: CD163-expressing macrophages are abundant in ovarian cancer where they accelerate tumor growth and metastasis. CD47 blockade is a novel immunotherapy aiming to activate macrophage phagocytosis of tumor cells, but it is currently unknown if the tumor-associated macrophages expressing CD163 respond poorly to CD47 blockade. METHODS: Human monocyte-derived macrophages were exposed to tumor-conditioned medium from A2780 ovarian cancer cells during differentiation. Effects on gene expression, membrane protein levels, release of soluble proteins and macrophage phagocytosis of A2780 cells in response to CD47 blockade were measured and compared to control macrophages. RESULTS: Tumor cell conditioning induced macrophage expression of CD163 on both the mRNA and protein level. Furthermore, tumor conditioning simultaneously increased protein expression of the phenotype markers CD206 and CD80, and the phagocytosis checkpoint LILRB1. However, tumor conditioning did not reduce phagocytic capacity, as CD47 blockade induced macrophage phagocytosis of A2780 cells to similar degrees in both control and tumor cell-conditioned macrophages. DISCUSSION: In vitro tumor conditioning did not reduce the phagocytic response to CD47 blockade, suggesting that induction of a macrophage phenotype with increased expression of CD163 does not directly limit the capacity for phagocytosis of tumor cells. In conclusion, these findings suggest that CD163+ macrophages remain responsive to CD47 blockade, highlighting their potential as targets for immunotherapy in ovarian cancer.
Breast cancer stem cells convert anti-tumor CD4 T cells to pro-tumor T regulatory cells: Potential role of exosomal FOXP3.
Basak U, Chakraborty S, Mukherjee S … +7 more , Pati S, Khan P, Ghosh S, Adhikary A, Jana K, Sa G, Das T
Cell Immunol · 2025 · PMID 39983598 · Publisher ↗
Cancer progression and its treatment-response are regulated by the tumor microenvironment (TME). Tumor-initiating cancer stem cells (CSCs) remain in constant communication with the TME, and modulate it through several me...
Cancer progression and its treatment-response are regulated by the tumor microenvironment (TME). Tumor-initiating cancer stem cells (CSCs) remain in constant communication with the TME, and modulate it through several mechanisms. Here, from in-silico findings and analyzing breast cancer patient tissue-derived data, CSCs and Tregs were found to be positively correlated. Furthermore, our in-silico analyses highlighted a positive relationship between CSC genes and Treg signature marker, FOXP3, even in cancer cell lines that do not contain any T cell or Treg cells, thus raising the possibility of CSCs expressing FOXP3. Validating our hypothesis, higher expression of FOXP3, both at mRNA and protein levels, was observed in breast CSCs than non-stem cancer cells. Since a small population of CSCs initiate tumor in immune cell-dominated TME, we aimed at exploring whether breast CSCs directly transfer FOXP3 to CD4T cells to generate immunosuppressive Treg cells. First, our search revealed CSC-derived exosomes (CDEs) generated CD4CD25FOXP3 Tregs at an early time-point of 24 h, which were immunosuppressive in nature. Next, detecting presence of FOXP3 protein in CDEs showed a strong possibility of FOXP3 transfer through CDEs. This was supported by detecting elevated FOXP3 levels from 12 h in translation inhibitor-treated T cells upon CDE-exposure. Finally, exosomes derived from FOXP3 attenuated-CSCs furnished lower FOXP3 in T cells than control CDEs. This mechanism was validated in in-vivo murine model. Together these results indicate a hitherto unexplored role of CSC-derived FOXP3 in reprogramming T cells into immunosuppressive Treg cells.
Tim-3 promotes viral infection by suppressing the USP25-TRAF3-IRF7 signaling pathway.
Du L, Chen J, Du C … +13 more , Chen J, Wang Z, Bao B, Zhonglin LV, Xing C, Liang M, Wang L, Xie S, Li Y, Wang Z, Li G, Zhang J, Han G
Cell Immunol · 2025 · PMID 39946759 · Publisher ↗
Tim-3, an immune checkpoint inhibitor, plays key roles in maintaining immune homeostasis and is involved in viral evasion. However, the precise role of Tim-3 in viral infection remains to be determined. USP25 is a deubiq...
Tim-3, an immune checkpoint inhibitor, plays key roles in maintaining immune homeostasis and is involved in viral evasion. However, the precise role of Tim-3 in viral infection remains to be determined. USP25 is a deubiquitinating enzyme that initiates antiviral immunity by deubiquitinating TRAF3 and triggering the antiviral signaling pathway. Here we found that Tim-3-specific knockout in myeloid cells leads to enhanced antiviral immunity in mice with vesicular stomatitis virus (VSV) encephalitis by increasing the type I interferon response. Mechanistically, Tim-3 inhibits the expression of USP25 via STAT1 and interacts with USP25 but does not regulate its posttranslational modification; as a result, Tim-3 inhibits USP25-mediated deubiquitination of TRAF3, promotes K48-linked ubiquitination and degradation of TRAF3, inhibits the phosphorylation of IRF7, and ultimately downregulates the interferon response. These findings provide new insights into the function of Tim-3 in antiviral immunity and its related clinical significance.
The polarization of macrophages participates in the repair after folic acid-induced acute kidney injury.
Yang S, Shen Y
Cell Immunol · 2025 · PMID 39933418 · Publisher ↗
Acute kidney injury (AKI) remains a major public health challenge, posing serious threats to human health. Increasing evidence indicates that renal cells undergo significant metabolic alterations following AKI, with infl...
Acute kidney injury (AKI) remains a major public health challenge, posing serious threats to human health. Increasing evidence indicates that renal cells undergo significant metabolic alterations following AKI, with inflammatory responses persisting throughout both injury and repair phases. Our previous research has demonstrated that heightened aerobic glycolysis after AKI leads to increased secretion of metabolic byproducts such as lactate, which plays a critical role in tissue repair. However, the relationship between metabolic reprogramming and inflammatory responses, as well as the underlying mechanisms, remain poorly understood. This study aims to clarify the regulatory effects of the glycolytic byproduct lactate on macrophage activation and phenotypic differentiation following AKI. We observed increased expression of M1/M2 macrophages and elevated secretion of inflammatory cytokines after folic acid-induced AKI. Immunofluorescence staining showed co-localization of macrophages with α-SMA. Manipulating lactate levels post-injury led to a decrease in macrophage expression and a reduction in fibroblast activation and proliferation, ultimately impairing renal tissue repair. These findings suggest that targeting lactate as a key regulator of macrophage phenotype differentiation may provide a theoretical and clinical foundation for therapeutic strategies in AKI repair.
The double-edged sword role of natural Killer cells in Parkinson's disease.
Daneshjou D, Nabavi SM, Shams P … +3 more , Faranoush P, Salari M, Ebrahimi M
Cell Immunol · 2025 · PMID 39864276 · Publisher ↗
Neurological disorders are the leading cause of disability worldwide, with Parkinson's disease (PD) emerging as a rapidly growing neurological condition on a global scale. Although treatments exist to alleviate symptoms...
Neurological disorders are the leading cause of disability worldwide, with Parkinson's disease (PD) emerging as a rapidly growing neurological condition on a global scale. Although treatments exist to alleviate symptoms and maintain patients' quality of life, PD remains incurable. According to some recent studies, natural killer (NK) cells may play a role in clearing alpha-synuclein aggregates, which are the main component of Lewy bodies that cause neuronal degeneration in Parkinson's disease. NK cells may also have an adverse impact on this condition by modulating inflammation and antigen-presenting cell function. Modifying NK cells derived from diverse sources, such as umbilical cord blood, presents a promising avenue for immunotherapy in PD patients, particularly during the early stages of the condition. Consequently, further research is essential to elucidate the mechanisms by which NK cells operate in Parkinson's patients and to assess their viability as potential biomarkers or therapeutic targets.
Arctiin suppress Th17 cells response and ameliorates experimental autoimmune uveitis through JAK/STAT signaling.
Fan X, Xu M, Wang Z … +6 more , Sun X, Fan Y, Chen J, Hao J, Wang R, Jia W
Cell Immunol · 2025 · PMID 39862562 · Publisher ↗
Conventional treatments for autoimmune uveitis, such as corticosteroids and systemic immunosuppressants, often result in adverse side effects, prompting the need for therapies targeting specific molecular pathways. This...
Conventional treatments for autoimmune uveitis, such as corticosteroids and systemic immunosuppressants, often result in adverse side effects, prompting the need for therapies targeting specific molecular pathways. This study investigates the effects of Arctiin, known for its diverse biological properties, on experimental autoimmune uveitis (EAU) through its action on Th17 cells and the JAK/STAT signaling pathway. Our findings reveal that Arctiin significantly alleviates EAU by reducing clinical scores, inflammatory cell infiltration, and levels of inflammatory cytokines like IL-17 and TNF-α in the eye. Arctiin achieves this by activating adiponectin receptor 1 (AdipoR1), which modulates the JAK/STAT pathway, thereby inhibiting Th17 cell differentiation and cytokine secretion. Additionally, Arctiin effectively suppresses IRBP-specific Th17 cell activation in cervical lymph nodes, further mitigating retinal inflammation and tissue damage. These results underscore Arctiin's potential as a therapeutic agent for uveitis and other autoimmune inflammatory disorders through the modulation of the AdipoR1/JAK/STAT pathway in Th17 cells.
Effect of high-fat diet on IgA cells and BAFF/APRIL in small intestinal villous lamina propria of mice.
Sakamoto Y, Niwa M, Muramatsu K … +1 more , Shimo S
Cell Immunol · 2025 · PMID 39842230 · Publisher ↗
Obesity exacerbates susceptibility to infectious diseases. We investigated the effects of a high-fat diet (HFD) on intestinal immunity, particularly immunoglobulin (Ig)A-producing cells, B-cell activating factor (BAFF),...
Obesity exacerbates susceptibility to infectious diseases. We investigated the effects of a high-fat diet (HFD) on intestinal immunity, particularly immunoglobulin (Ig)A-producing cells, B-cell activating factor (BAFF), and a proliferation-inducing ligand (APRIL) localization. Mice (4- to 20-weeks old) were fed HFD or standard chow diet, and their jejunum and ileum were fixed using the in vivo cryotechnique. Immunohistochemistry was performed for IgA, BAFF, and APRIL. In the HFD group, IgA, IgACD22 (p < 0.001), and IgACD138 (p = 0.007) cell counts were diminished in the middle sections of the lamina propria of jejunal villi, and BAFF levels were significantly reduced in jejunal villi. The HFD effects on IgA cell distribution seem to be confined to jejunal villi, hinting at localized vulnerabilities in intestinal immunity during obesity. Moreover, in the HFD group, IgA B-cell counts were reduced in the middle jejunum, indicating inhibition of the IgA B-cells through a T-cell-independent pathway.
IL-17 family members exert an autocrine pro-inflammatory loop in CF respiratory epithelial cells ex vivo.
Allegretta C, Montemitro E, Ciciriello F … +6 more , Altieri MT, Sabbioni G, Breveglieri G, Borgatti M, Cabrini G, Laselva O
Cell Immunol · 2025 · PMID 39837005 · Publisher ↗
BACKGROUND: Lungs of people with Cystic Fibrosis (pwCF) are characterized by chronic inflammation and infection with P. aeruginosa. High levels of IL-17 A and F have been observed in sputum of pwCF and the interleukin-17...
BACKGROUND: Lungs of people with Cystic Fibrosis (pwCF) are characterized by chronic inflammation and infection with P. aeruginosa. High levels of IL-17 A and F have been observed in sputum of pwCF and the interleukin-17(IL-17) family (A-to-F) has been suggested to play a key role in CF pulmonary disease. METHODS: We measured mRNA levels of IL-17 receptors (IL-17R) by RT-qPCR in CF bronchial epithelial (CFBE) cultured cells upon infection with P. aeruginosa PAO1 strain or clinical exoproducts (EXO) isolated from pwCF. We measured IL-17 mRNA expression by RT-qPCR and the release of cytokines by ELISA and Bioplex from CF primary nasal epithelial (HNE) cultured cells. RESULTS: Infection of CFBE cells with PAO1 or EXO isolated from 15 pwCF significantly increased mRNA expression of all IL-17R, except IL-17RD. Infection of HNE cells with EXO isolated from the correspondent donor significantly increased the mRNA levels of all the IL-17 cytokines and receptors, except for IL-17D and IL-17RD, and the release of the cytokines IL-17 A, IL-17B, IL-17C, IL-17E and IL-17F. HNE exposed to IL-17 A and F were induced to release pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), neutrophil chemokines (IL-8, G-CSF) and cytokines known to be involved in chloride and bicarbonate secretion, together with mucin upregulation (IL-4, IL-13). CONCLUSION: These results highlight a wider expression of IL-17 family member in respiratory epithelial cells, which can play a role as an autocrine inflammatory amplification loop in CF airways. These in-vitro studies using patient-derived cultures underline the relevant role of IL-17 family members in CF pulmonary immune response.
The distinct characteristic of two peritoneal macrophage subsets in a mouse model of hepatocellular carcinoma presents a novel therapeutic strategy.
Yang WL, Yang C, Pang N … +3 more , Yu RH, Tong KY, Jiang F
Cell Immunol · 2025 · PMID 39824005 · Publisher ↗
The peritoneal cavity (PerC) is a discrete anatomical compartment housing diverse peritoneal macrophage subpopulations. Nonetheless, there exists a paucity of knowledge concerning the distinct functions of these subpopul...
The peritoneal cavity (PerC) is a discrete anatomical compartment housing diverse peritoneal macrophage subpopulations. Nonetheless, there exists a paucity of knowledge concerning the distinct functions of these subpopulations in the context of hepatocellular carcinoma (HCC) and their evolution throughout tumor advancement. This investigation seeks to analyze the characteristics of two principal peritoneal macrophage subpopulations, specifically large peritoneal macrophage (LPM) and small peritoneal macrophage (SPM), in the context of HCC. The results of our research indicate a significant decrease in the proportion of LPM during the progression of HCC, accompanied by an increase in the quantity of SPM. Furthermore, SPM found in ascites exhibited a macrophage phenotype that supports tumor growth in HCC. Importantly, the dynamic decrease of LPM in murine models following lipopolysaccharide (LPS) stimulation led to a decrease in survival rate, highlighting the critical role of the altered LPM to SPM ratio in HCC survival. By employing clodronate liposomes (CL) to deplete peritoneal macrophage in murine models, followed by the adoptive transfer of LPM, we effectively prolonged the survival of HCC and attenuated tumor progression. Our results suggest that a decrease in the LPM to SPM ratio correlates with increased mortality in the HCC model. On the contrary, the maintenance of a high ratio of LPM to SPM has shown a positive effect on HCC survival. These findings have enhanced our understanding of the complex interaction between different subpopulations of peritoneal macrophage in the development of HCC. Furthermore, these results have important implications for the development of novel therapeutic strategies.
KLHDC8A knockdown in normal ovarian epithelial cells promoted the polarization of pro-tumoral macrophages via the C5a/C5aR/p65 NFκB signaling pathway.
Fang J, Wang J, Zhao X … +2 more , Yang Y, Xiao Y
Cell Immunol · 2025 · PMID 39805213 · Publisher ↗
AIMS: Tumor-associated macrophages (TAM) is related to Ovarian cancer (OC) pathogenesis, but the exact mechanism remains unclear. This study investigated the expression of Kelch Domain Containing 8 A (KLHDC8A) in OC and...
AIMS: Tumor-associated macrophages (TAM) is related to Ovarian cancer (OC) pathogenesis, but the exact mechanism remains unclear. This study investigated the expression of Kelch Domain Containing 8 A (KLHDC8A) in OC and the mechanism associated with TAM. MAIN METHODS: Bioinformatics analysis of differential expression genes between normal and OC tissues were analyzed based on the Tumor Genome Atlas (TCGA) databases. KLHDC8A mRNA expression was knocked down in normal epithelial cells (IOSE80), and then the effects of siKLHDC8A on the proliferation, invasion, migration and C5a secretion of IOSE80 cells were explored. THP1-derived macrophages were cultured with medium of NC-IOSE80 cells, siKLHDC8A-IOSE80 cells with or without C5aR antagonists. KEY FINDINGS: KLHDC8A was lowly expressed in OC and negatively correlated with the infiltration of tumor-promoting macrophages, contributing to the survival of OC patients. Furthermore, siKLHDC8A promotes the proliferation, invasion and migration of IOSE80 cells and leads to polarization of pro-tumoral macrophages, which can be rescued by C5aR antagonists. SIGNIFICANCE: Our results indicated that KLHDC8A knockdown could modulate the development of OC by affecting macrophage polarization to pro-tumoral type via the C5a/C5aR/p65 NFκB signaling pathway. It may play an essential role as the tumor suppressor genes in diagnosis and treatment of OC.
Deciphering the role of TMEM164 in autophagy-mediated ferroptosis and immune modulation in non-small cell lung cancer.
ALMatrafi TA
Cell Immunol · 2025 · PMID 39798196 · Publisher ↗
BACKGROUND: Non-small cell lung cancer (NSCLC) remains one of the most prevalent and deadly malignancies. Despite advancements in molecular therapies and diagnostic methods, the 5-year survival rate for lung adenocarcino...
BACKGROUND: Non-small cell lung cancer (NSCLC) remains one of the most prevalent and deadly malignancies. Despite advancements in molecular therapies and diagnostic methods, the 5-year survival rate for lung adenocarcinoma patients remains unacceptably low, highlighting the urgent need for novel therapeutic strategies. Ferroptosis, a distinct form of regulated cell death, has emerged as a promising target in cancer treatment. This study investigates the role of TMEM164, a membrane protein, in promoting ferroptosis and modulating anti-tumor immunity in NSCLC, aiming to elucidate its therapeutic potential. METHODS: Using publicly available datasets, we performed bioinformatics analyses to identify TMEM164-regulated genes involved in ferroptosis. In addition, in vitro and in vivo assays were conducted to assess the impact of TMEM164 on cellular functions in NSCLC. RESULTS: Functional assays demonstrated that TMEM164 overexpression significantly inhibited invasion, migration, and cell proliferation in both in vitro and in vivo models. TMEM164 was also found to induce ferroptosis in NSCLC cells by promoting autophagy. Specifically, we identified a mechanism whereby TMEM164 mediates ATG5-dependent autophagosome formation, leading to the degradation of ferritin, GPX4, and lipid droplets. This degradation facilitated iron accumulation and lipid peroxidation, which triggered iron-dependent cell death. Notably, co-administration of TMEM164 upregulation and anti-PD-1 antibodies exhibited synergistic anti-tumor effects in a mouse model. CONCLUSION: These findings suggest that targeting TMEM164 to enhance ferroptosis and stimulate anti-tumor immunity may inhibit NSCLC progression. Consequently, TMEM164 holds promise as a new therapeutic target for NSCLC treatment.
Bacteriophage derived dsRNA induces polarized activation of alveolar macrophages from Balb/c and C57Bl/6 mice in vitro in sex- and age-dependent manner.
Dovhyi R, Dvukhriadkina A, Ostrovska K … +6 more , Rudyk M, Verhovcova I, Vaivode K, Pjanova D, Ostapchenko L, Skivka L
Cell Immunol · 2025 Feb · PMID 39787694 · Publisher ↗
Bacteriophage-derived dsRNA (bp-dsRNA), also known as Larifan, is a poly-functional and wide-spectrum antiviral medication with potent interferonogenic activity. In the lungs of golden Syrian hamsters infected with SARS-...
Bacteriophage-derived dsRNA (bp-dsRNA), also known as Larifan, is a poly-functional and wide-spectrum antiviral medication with potent interferonogenic activity. In the lungs of golden Syrian hamsters infected with SARS-CoV-2, Larifan substantially reduces viral load and decreases infection-induced pathological lesion severity. Alveolar macrophages (AM) are key sentinel cells in the lung, which play an important role in antiviral innate immune responses and, at the same time, can trigger infection-associated hyper-inflammatory response. This study revealed that treatment with bp-dsRNA (Larifan) in vitro modulates the functional profile of AM from intact Balb/c and C57Bl/6 mice. The pattern of the drug response depends on the animal strain, age and sex. AM from Balb/c mice generated a weaker response to the preparation as compared to cells from C57Bl/6 mice. Most emphatic responses to the treatment with bf-dsRNA (Larifan) were registered in AM from old males of both BALB/c and C57BL/6 strains with the strongest in the latter. AM from old C57BL/6 females were less likely to be influenced by the preparation. In most cases, exposure to bf-dsRNA (Larifan) increased AM phagocytic activity and was more often accompanied by the stimulation of intracellular reactive oxygen species generation, than by its decrease. In most animal groups, treatment with bf-dsRNA (Larifan) did not affect significantly CD206 expression and down-regulated CD80 expression in AM. Taken together, our findings suggest that bf-dsRNA (Larifan) not so much stimulates the bivalent phenotype of AM, as restrains their hyper-inflammatory responses through the control of antigen-presentation while preserving functional signatures typical of patrolling tissue-resident macrophages.
The effect of tocilizumab treatment for skin fibrosis by inhibiting CD38 macrophages in systemic sclerosis.
Chen H, Yang D, Shi Y … +5 more , Wu H, Zhu H, Jiang T, Liu S, Wang D
Cell Immunol · 2025 Feb · PMID 39778381 · Publisher ↗
BACKGROUND: Dermal and pulmonary fibrosis are the main clinical symptoms of systemic scleroderma (SSc), for which there are no effective therapeutic agents. Tocilizumab is thought to improve the symptoms of fibrosis, but...
BACKGROUND: Dermal and pulmonary fibrosis are the main clinical symptoms of systemic scleroderma (SSc), for which there are no effective therapeutic agents. Tocilizumab is thought to improve the symptoms of fibrosis, but the effect of tocilizumab on dermal fibrosis has not been explored. This study aims to investigate the therapeutic effect of tocilizumab on skin fibrosis by inhibiting CD38 macrophages in the bleomycin-induced SSc mice model. METHODS: The 8-week-old BALB/c mice were randomly divided into three groups: control group (PBS group), model group (BLM group), and tocilizumab group (TCZ group). The mRNA expression of VIMENTIN, TIMP1, and COL1A1 was measured by qPCR. Western blot was used to detect the protein expression of α-SMA, TGF-β, and COL1A1 in skin tissues. The expression of CD38 macrophages in the BLM-induced fibrosis mouse model was verified by flow cytometry and immunofluorescence. RESULTS: In comparison to the PBS control group, mice in the BLM group showed skin fibrosis, edema, thickness, and collagen deposition. The percentage of macrophages in the skin, peripheral blood, and spleen was significantly increased in the BLM group, and the percentage of CD38 macrophages increased in the skin and peripheral blood but decreased in the spleen. After co-cultured with macrophages, L929 fibroblasts differentiated into myofibroblasts, with increased mRNA expression of COL1A1, COL3A, TGF-β, and Fibronectin. Furthermore, after being stimulated by LPS, RAW264.7 cells showed increased expression of IL-6 and CD38. The mRNA levels of COL1A1, COL1A2, COL3A, TGF-β, and Fibronectin in L929 fibroblasts were markedly increased when co-cultured with LPS-stimulated RAW264.7 cells. Tocilizumab treatment reduced dermal thickness and collagen deposition induced by BLM. Furthermore, the percentage of total macrophages and CD38 macrophages in the skin and peripheral blood significantly decreased after tocilizumab treatment. CONCLUSION: This study revealed that tocilizumab improved skin fibrosis in the SSc mice model, which was mediated by inhibiting skin and peripheral CD38 macrophages.
Sodium butyrate prevents lipopolysaccharide induced inflammation and restores the expression of tight junction protein in human epithelial Caco-2 cells.
Bakshi J, Mishra KP
Cell Immunol · 2025 Feb · PMID 39729961 · Publisher ↗
The gastrointestinal (GI) tract is susceptible to damage under high altitude hypoxic conditions, leading to gastrointestinal discomfort and intestinal barrier injury. Sodium butyrate, a short-chain fatty acid present as...
The gastrointestinal (GI) tract is susceptible to damage under high altitude hypoxic conditions, leading to gastrointestinal discomfort and intestinal barrier injury. Sodium butyrate, a short-chain fatty acid present as a metabolite in the gut, has emerged as a promising therapeutic agent due to its ability to act as an immunomodulatory agent and restore intestinal barrier integrity. This study aimed to explore the mechanism by which sodium butyrate exhibits anti inflammatory effect on intestinal epithelial cells. In vitro, Caco-2 epithelial cells and RAW 264.7 macrophages were used to investigate the protective role of sodium butyrate on Lipopolysaccharide (LPS) induced inflammation. Cell viability assays demonstrated that 1 mM (110.86 μg/mL) of sodium butyrate did not exhibit cytotoxicity on cells in vitro. Treatment with sodium butyrate suppressed reactive oxygen species levels and TNF-α production in LPS-stimulated macrophages, indicating its efficacy in mitigating inflammatory responses. Western blot analysis revealed that sodium butyrate attenuated the expression of iNOS in RAW 264.7 macrophage cells. Moreover, sodium butyrate also reversed the LPS induced over expression of HIF-1α, NLRP3, IL-1β as well as NF-kB in Caco-2 epithelial cells and also had a suppressive effect on IL-8 secretion after LPS stimulation. Immunocytochemistry demonstrated that sodium butyrate enhanced tight junction protein occludin expression in Caco-2 cells while also restoring the decreased permeability of the Caco-2 monolayer due to LPS. These results indicate that sodium butyrate may influence immune responses by suppressing inflammatory mediators and improving the integrity of the epithelial barrier. Understanding the intricate interactions between gut metabolites and host immune responses may help in the development of innovative therapeutic strategies to alleviate intestinal inflammation in high altitude environments.
Augmented IFNγ producing ILC1 and IL 17 producing ILC3 in pemphigus vulgaris: Plausible therapeutic target.
Hooda V, Khandpur S, Sharma A
Cell Immunol · 2025 Feb · PMID 39718308 · Publisher ↗
Innate Lymphoid cells (ILCs) are innate counterparts of helper T cells. Although low in number, they have proven to play major roles in many autoimmune diseases. In Pemphigus Vulgaris (PV), the gaps in the knowledge of f...
Innate Lymphoid cells (ILCs) are innate counterparts of helper T cells. Although low in number, they have proven to play major roles in many autoimmune diseases. In Pemphigus Vulgaris (PV), the gaps in the knowledge of functional role of ILCs remain. To bridge the gap, our study investigated the phenotype along with the functional determinants of ILCs involved in PV immunopathogenesis. Our data suggested augmentation in overall ILC population in circulation of PV patients. Specifically, ILC1 and ILC3 subtypes were significantly increased in peripheral circulation of PV patients compared to healthy controls. We observed no changes in ILC2 population. mRNAs from ILC enriched population showed significant upregulation in transcription factors- ID2, T bet and RORγt and a downregulation in GATA3 and RORα. The mRNA levels of ILC related cytokines- IFNγ and IL17 were significantly upregulated while no change was observed in the levels of IL13, IL 22, AHR. The levels of autoantibodies against desmoglein (Dsg) 3 which is the characteristic of PV pathogenesis were also checked in the serum which confirmed significant upregulation in PV patients. The levels of proinflammatory- IFNγ, IL 17 and IL 15 were elevated and anti-inflammatory cytokines- IL10 was downregulated in the serum of PV patients. The results of this study offer insights into the functional attributes of ILCs and related cytokines, potentially contributing to the development of future therapeutic interventions.
Enhanced apoptosis and inflammation allied with autophagic and apoptotic Leishmania amastigotes in the seemingly undamaged ear skin of clinically affected dogs with canine visceral Leishmaniasis.
Verçosa BLA, Muniz-Junqueira MI, Mineiro ALBB … +2 more , Melo MN, Vasconcelos AC
Cell Immunol · 2025 Feb · PMID 39701006 · Publisher ↗
Programmed cell death plays a relevant role in the pathogenesis of visceral Leishmaniasis. Apoptosis selects suitable parasites, regulating parasite density, whereas autophagy eliminates pathogens. This study aimed to as...
Programmed cell death plays a relevant role in the pathogenesis of visceral Leishmaniasis. Apoptosis selects suitable parasites, regulating parasite density, whereas autophagy eliminates pathogens. This study aimed to assess the inflammation and apoptosis in inflammatory cells and presents a unique description of the presence of autophagic and apoptotic Leishmania amastigotes in naturally Leishmania-infected dogs. Fragments from seemingly undamaged ear skin of sixteen Leishmania-infected dogs and seven uninfected dogs were evaluated through histomorphometry, ultrastructural, immunohistochemical and transmission electron microscopy (TEM) analyses. Leishmania amastigotes were present on seemingly undamaged ear skin only in clinically affected dogs. Parasite load, morphometrical parameters of inflammation and apoptotic index of inflammatory cells were higher in clinically affected animals and were related to clinical manifestations. Apoptotic index and morphometric parameters of the inflammatory infiltrate in undamaged ear skin were positively correlated with parasite load. Apoptotic and non-apoptotic Leishmania amastigotes were observed within neutrophils and macrophages. Leishmania amastigotes were positive for Bax, a marker for apoptosis, by immunohistochemistry. Morphological characteristics of apoptosis and autophagy in Leishmania amastigotes were observed only in phagocytes of clinically affected dogs. Positive correlations were found between histomorphometry and clinical manifestations. Our results showed that apoptosis and autophagy in Leishmania amastigotes may be related to both the increase in parasite load and apoptotic index in inflammatory cells, and with the intensity of the inflammatory response in clinically affected dogs. Thus, our study suggests that apoptotic and autophagy Leishmania within phagocytes may have facilitate the survival of the parasite and it appears to play an important role in the process of Leishmania infection.
Berberine shaping the tumor immune landscape via pyroptosis.
Xie J, Du X, Li Y … +4 more , Wu C, Li R, Zhao M, Shi S
Cell Immunol · 2025 Feb · PMID 39701005 · Publisher ↗
Pyroptosis is a programmed cell death (PCD) mainly mediated by the Gasdermin family of proteins, among which Gasdermin E (GSDME) is considered a tumor suppressor gene. GSDME can recruit immune cells to the tumor microenv...
Pyroptosis is a programmed cell death (PCD) mainly mediated by the Gasdermin family of proteins, among which Gasdermin E (GSDME) is considered a tumor suppressor gene. GSDME can recruit immune cells to the tumor microenvironment (TME) and promote their effects. Activating and enhancing adaptive immunity through GSDME is a potential solution for anti-tumor therapy. Here we reported that berberine (BBR), a small molecule from traditional Chinese medicine, as a GSDME activator, induced caspase-3 (C-3)/GSDME pathway-mediated pyroptosis through the mitochondrial pathway, improved the immunosuppressive state of the tumor microenvironment, and thus promoted anti-tumor immunity. We determined the induction of pyroptosis of 4 T1 cells by BBR through various experiments, and investigated the immune activation effect of BBR by co-culture in vitro, which induced DCs maturation and macrophage polarization. Zebrafish embryo toxicity experiments were used to evaluate the in vivo safety of berberine. Furthermore, the in vivo antitumor and immune activation effects of BBR were investigated using 4 T1 orthotopic model mice, and the results showed that BBR could eliminate orthotopic tumor cells by activating local and systemic immunity. Moreover, we observed that BBR significantly inhibited breast cancer lung metastasis. In summary, our results showd the role of BBR as a GSDME activator stimulated both local and systemic antitumor immune responses by inducing pyroptosis, effectively preventing tumor development and metastasis.
P2RX1-blocked neutrophils induce CD8 T cell dysfunction and affect the immune escape of gastric cancer cells.
Zhang Y, Zhang F, Liu Z … +3 more , Li M, Wu G, Li H
Cell Immunol · 2025 Feb · PMID 39675308 · Publisher ↗
BACKGROUND: Gastric cancer (GC) is one of the deadly malignancies of the gastrointestinal tract. Research has confirmed the linkage of P2RX1 with immune cell activation and tumor progression. This project focused on the...
BACKGROUND: Gastric cancer (GC) is one of the deadly malignancies of the gastrointestinal tract. Research has confirmed the linkage of P2RX1 with immune cell activation and tumor progression. This project focused on the impact of P2RX1 level in neutrophils on the efficacy of immune checkpoint inhibitor (ICI) treatment in GC. METHODS: Blood samples from 23 GC patients eligible for camrelizumab treatment were collected. Flow cytometry was carried out to analyze the proportion of P2RX1 in neutrophils. IHC was utilized to detect the expression level of PD-L1. We also evaluated the chemotaxis ability of neutrophils using a Transwell system, assessed the viability and apoptosis rate of GC cells using CCK-8 and flow cytometry, measured the proportions of CD8PD-1 and CD8GZMB cells, determined the expression levels of IL-6, TNFα, IFN-γ, IL-8, IL-12, IL-1β, and GZMB by utilizing enzyme-linked immunosorbent assay (ELISA), and examined the expression levels of P2RX1 and PD-L1 using western blot (WB). By establishing a xenograft mouse model, we studied the impact of P2RX1-blocked neutrophils on the efficacy of ICI treatment in the GC microenvironment. RESULTS: In GC, clinical analysis revealed increased infiltration of P2RX1-lowly expressed neutrophil subsets and increased expression of PD-L1. In vitro experiments demonstrated that abnormal expression of P2RX1 affected neutrophil function. Furthermore, the blockage or knockdown of P2RX1 in neutrophils modulated CD8 T cell function, promoting GC progression. In in vivo experiments, the blockage of P2RX1 in neutrophils inhibited the effectiveness of ICI treatment in the GC microenvironment. CONCLUSION: This project validated that the loss of P2RX1 in neutrophils induces CD8 T cell dysfunction and affects the GC development, indicating that P2RX1 may be an accurate biomarker for predicting ICI response, thus providing a theoretical basis for the clinical application of ICI.
Natural killer cell-based therapies in neuroblastoma.
Ghasempour A, Mohseni R, Sharif PM … +1 more , Hamidieh AA
Cell Immunol · 2025 Jan · PMID 39631142 · Publisher ↗
Neuroblastoma (NB) is the most common extracranial solid tumor of childhood forming around 15 % of all pediatric tumors. Despite advances in the treatment of NB, high-risk patients still face a grave prognosis. Adoptive...
Neuroblastoma (NB) is the most common extracranial solid tumor of childhood forming around 15 % of all pediatric tumors. Despite advances in the treatment of NB, high-risk patients still face a grave prognosis. Adoptive cell therapies based on NK cells are becoming an assistive treatment for such cases. Moreover, there is also evidence that NKT-based therapies have promising results in the management of NB. Lower complications in comparison with adoptive T cell therapies, various cell sources, and miscellaneous tumor recognition mechanisms are some of the advantages of NK- and NKT-based therapies. This review is dedicated to searching for recent advances in this field.
The CCL5/CCR5 axis in ulcerative colitis.
Qu FF, Wu YQ, Ji JB … +6 more , Yan L, Wei JJ, Song QC, Xu BQ, Cheng M, Zhou ZH
Cell Immunol · 2025 Jan · PMID 39608128 · Publisher ↗
Ulcerative colitis (UC) is a chronic nonspecific inflammatory bowel disease characterized mainly by inflammatory changes in the intestinal mucosa. While the specific etiology of UC remains unclear, it is generally believ...
Ulcerative colitis (UC) is a chronic nonspecific inflammatory bowel disease characterized mainly by inflammatory changes in the intestinal mucosa. While the specific etiology of UC remains unclear, it is generally believed that it is related to many factors, among which the imbalance in the expression of molecules involved in pro-inflammatory and anti-inflammatory processes can lead to UC. CCL5 (C-C chemokine ligand 5) is one of the key pro-inflammatory factors and plays an indispensable role in various inflammatory diseases, including UC. CCL5 binds and activates the receptor CCR5 (C-C chemokine receptor type 5), which in turn, promotes signaling pathways such as PI3K/AKT, NF-κB, and Ras/MAPK, playing an important role in the pathogenesis of UC. The focus of this paper is on the function of the CCL5/CCR5 axis and its subsequent signaling pathways in UC therapy. In addition to this, the article further explores the possible healing benefits of CCR5 antagonists and agonists aimed at the CCL5/CCR5 axis for UC treatment.
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