Cellular Immunology[JOURNAL]
Sun
200 papers
HIF-1α is required to differentiate the neonatal Macrophage protein secretome from adults.
Becker A, Filipp M, Lantz C … +2 more , Glinton K, Thorp EB
Cell Immunol · 2024 · PMID 39098245 · Publisher ↗
The immune response to stress diverges with age, with neonatal macrophages implicated in tissue regeneration versus tissue scarring and maladaptive inflammation in adults. Integral to the macrophage stress response is th...
The immune response to stress diverges with age, with neonatal macrophages implicated in tissue regeneration versus tissue scarring and maladaptive inflammation in adults. Integral to the macrophage stress response is the recognition of hypoxia and pathogen-associated molecular patterns (PAMPs), which are often coupled. The age-specific, cell-intrinsic nature of this stress response remains vague. To uncover age-defined divergences in macrophage crosstalk potential after exposure to hypoxia and PAMPs, we interrogated the secreted proteomes of neonatal versus adult macrophages via non-biased mass spectrometry. Through this approach, we newly identified age-specific signatures in the secretomes of neonatal versus adult macrophages in response to hypoxia and the prototypical PAMP, lipopolysaccharide (LPS). Neonatal macrophages secreted proteins most consistent with an anti-inflammatory, regenerative phenotype protective against apoptosis and oxidative stress, dependent on hypoxia inducible transcription factor-1α (HIF-1α). In contrast, adult macrophages secreted proteins consistent with a pro-inflammatory, glycolytic phenotypic signature consistent with pathogen killing. Taken together, these data uncover fundamental age and HIF-1α dependent macrophage responses that may be targeted to calibrate the innate immune response during stress and inflammation.
R406 reduces lipopolysaccharide-induced neutrophil activation.
Warner S, Teague HL, Ramos-Benitez MJ … +11 more , Panicker S, Allen K, Gairhe S, Moyer T, Parachalil Gopalan B, Douagi I, Shet A, Kanthi Y, Suffredini AF, Chertow DS, Strich JR
Cell Immunol · 2024 · PMID 39084187 · Full text
Modulating SYK has been demonstrated to have impacts on pathogenic neutrophil responses in COVID-19. During sepsis, neutrophils are vital in early bacterial clearance but also contribute to the dysregulated immune respon...
Modulating SYK has been demonstrated to have impacts on pathogenic neutrophil responses in COVID-19. During sepsis, neutrophils are vital in early bacterial clearance but also contribute to the dysregulated immune response and organ injury when hyperactivated. Here, we evaluated the impact of R406, the active metabolite of fostamatinib, on neutrophils stimulated by LPS. We demonstrate that R406 was able to effectively inhibit NETosis, degranulation, ROS generation, neutrophil adhesion, and the formation of CD16 neutrophils that have been linked to detrimental outcomes in severe sepsis. Further, the neutrophils remain metabolically active, capable of releasing cytokines, perform phagocytosis, and migrate in response to IL-8. Taken together, this data provides evidence of the potential efficacy of utilizing fostamatinib in bacterial sepsis.
ZFP36 family expression is suppressed by Th2 cells in asthma, leading to enhanced synthesis of inflammatory cytokines and cell surface molecules.
Uehara Y, Suzukawa M, Horie M … +5 more , Igarashi S, Minegishi M, Takada K, Saito A, Nagase H
Cell Immunol · 2024 · PMID 39067169 · Publisher ↗
Asthma is a chronic inflammatory airway disease, in which inflammatory cytokines play a pivotal role. The zinc finger binding protein 36 (ZFP36) family includes ZFP36, ZFP36L1, and ZFP36L2 and is among the RNA-binding pr...
Asthma is a chronic inflammatory airway disease, in which inflammatory cytokines play a pivotal role. The zinc finger binding protein 36 (ZFP36) family includes ZFP36, ZFP36L1, and ZFP36L2 and is among the RNA-binding proteins (RBPs) reported to cause inflammation. The present study aimed to clarify the roles of the ZFP36 family in asthma, particularly highlighting the relationship between the ZFP36 family and Th2 cells, which are key players in type 2 inflammation in asthma. Real-time PCR analysis revealed the preferential expression of ZFP36 family mRNAs in human white blood cells. Gene expression analysis using public datasets from the GEO database (https://www.ncbi.nlm.nih.gov/gds) showed significantly suppressed expression of ZFP36 family mRNAs in patients with asthma compared to that in healthy controls. Using multiple cytokine assays, Th2 cell transfection with ZFP36 family siRNAs enhanced the expression of inflammatory cytokines IL-8, IFN-γ, CCL3/MIP-1α, CCL4/MIP-1β, and TNF-α and cell surface molecules CCR4 (CD194) and PSGL-1 (CD162). Treatment with IL-2, 4, and 15 significantly suppressed, and corticosteroid significantly enhanced the expressions of ZFP36 family mRNAs by Th2 cells. In conclusion, the ZFP36 family expressed by Th2 cells was suppressed in patients with asthma, leading to the enhanced expression of cytokines and cell surface molecules. Suppressed ZFP36 expression in asthma may be involved in the enhancement of airway inflammation, and the ZFP36 family may be a therapeutic target for inflammatory diseases, including asthma.
Petunidin suppresses Hashimoto's thyroiditis by regulating Th1/Th17 homeostasis and oxidative stress.
Liu B, Li L, Wang X
Cell Immunol · 2024 · PMID 39053379 · Publisher ↗
Hashimoto's thyroiditis (HT) is a prevalent autoimmune thyroid disease, necessitating further research to identify effective treatment strategies. Two key pathophysiological factors of HT are inflammation and oxidative s...
Hashimoto's thyroiditis (HT) is a prevalent autoimmune thyroid disease, necessitating further research to identify effective treatment strategies. Two key pathophysiological factors of HT are inflammation and oxidative stress. Petunidin (PET) is an anthocyanin with anti-inflammatory and antioxidant properties. This study aimed to investigate the effect and mechanism of PET on HT. C57BL/6N mice were injected with thyroglobulin emulsified with adjuvant to establish the HT animal model. Our results showed that PET administration decreased the concentrations of TPOAb, TgAb, T3, T4, IgG, IgA and IgM in HT mice, accompanied by significant alterations in follicle shape and increased lymphocyte infiltrations. Additionally, the apoptosis rate, ROS level, MDA content, CD4+ level, IFN-γ and IL-17A levels, as well as the concentrations of IFN-γ and IL-17, were elevated in HT mice and reduced by PET treatment. Furthermore, HT patients exhibited higher levels of NOX4 and PKM2, which were positively correlated with TPOAb, IFN-γ, and IL-17 concentrations. In HT mice, PET therapy decreased the expression of PKM2 and NOX4 proteins. In summary, PET can improve thyroid dysfunction by suppressing apoptosis, oxidative stress and Th1/Th17 differentiation through regulation of the NOX4/PKM2 axis in HT mice, suggesting its promising potential for HT intervention.
Tumor micro-environment induced TRAIL secretion from engineered macrophages for anti-tumor therapy.
Zhu Q, Huang X, Deng B … +11 more , Guan L, Zhou H, Shi B, Liu J, Shan X, Fang X, Xu F, Li H, Liu X, Yin X, Zhang L
Cell Immunol · 2024 · PMID 39032210 · Publisher ↗
The high plasticity and long-term persistency make macrophages excellent vehicles for delivering anti-tumor cytokines. Macrophage delivery of chemokines and cytokines shows potential in tumor therapy. TRAIL, a promising...
The high plasticity and long-term persistency make macrophages excellent vehicles for delivering anti-tumor cytokines. Macrophage delivery of chemokines and cytokines shows potential in tumor therapy. TRAIL, a promising anti-tumor cytokine, induces apoptosis in tumor cells with low toxicity to normal cells. However, its off-target toxicity and limited stability have limited its clinical progress. Here, we engineered macrophages with Mono-TRAIL and Tri-TRAIL and found that Tri-TRAIL had higher cytotoxic activity against tumor cells than Mono-TRAIL in vitro. To target the tumor microenvironment (TME), we generated macrophages secreting trimeric TRAIL (Tri-TRAIL-iM) induced by the TME-specific promoter Arg1. The Tri-TRAIL-iM cells displayed high specific activatable activity in cell-based co-culture assay and tumor-baring mice models. In addition, we demonstrated that compared to macrophages over-expressing TRAIL under a non-inducible promoter, Tri-TRAIL-iM could more effectively induce apoptosis in cancer cells, inhibit tumor growth, and reduce systemic side effects. This strategy of inducing TRAIL delivery holds great potential for cancer therapy. It is promising to be combined with other engineering methods to maximize the therapeutic effects of solid tumors.
Yersinia pestis and pneumonic plague: Insight into how a lethal pathogen interfaces with innate immune populations in the lung to cause severe disease.
Venugopal G, Pechous RD
Cell Immunol · 2024 · PMID 39002222 · Publisher ↗
Yersinia pestis is the causative agent of bubonic, septicemic and pneumonic plague. The historical importance and potential of plague to re-emerge as a threat worldwide are indisputable. The most severe manifestion of pl...
Yersinia pestis is the causative agent of bubonic, septicemic and pneumonic plague. The historical importance and potential of plague to re-emerge as a threat worldwide are indisputable. The most severe manifestion of plague is pneumonic plague, which results in disease that is 100% lethal without treatment. Y. pestis suppresses host immune responses early in the lung to establish infection. The later stages of infection see the rapid onset of hyperinflammatory responses that prove lethal. The study of Y. pestis host/pathogen interactions have largely been investigated during bubonic plague and with attenuated strains in cell culture models. There remains a somewhat limited understanding of the interactions between virulent Y. pestis and immune populations in the lung that drive severe disease. In this review we give a broad overview of the progression of pneumonic plague and highlighting how Y. pestis interfaces with host innate immune populations in the lung to cause lethal disease.
Additional use of α-IgM antibodies potentiates CpG ODN2006-induced B cell activation by targeting mainly naïve and marginal zone-like B cells.
Fleige L, Fillatreau S, Claus M … +1 more , Capellino S
Cell Immunol · 2024 · PMID 38996539 · Publisher ↗
CpG ODN2006 is widely used as a potent B cell stimulant in vitro and in vivo. However, it shows a deficit in targeting naïve B cells in vitro. In this study, we investigated whether α-IgM can support ODN2006-induced effe...
CpG ODN2006 is widely used as a potent B cell stimulant in vitro and in vivo. However, it shows a deficit in targeting naïve B cells in vitro. In this study, we investigated whether α-IgM can support ODN2006-induced effects on B cells to obtain enhanced activation with focus on different B cell subsets. Our results delineated robust B cell activation, shown by increased activation marker expression and cytokine secretion by each agent alone, and further augmented when used in combination. Interestingly, α-IgM targeted mainly naïve and marginal zone-like B cells, thus complementing the pronounced effects of ODN2006 on memory B cells and achieving optimal activation for all B cell subsets. Taken together, combining ODN2006 and α-IgM is beneficial for in vitro activation including all B cell subsets. Furthermore, our results suggest that α-IgM could enhance efficacy of ODN2006 in vivo with further need of investigation.
CD147 regulates the formation and function of immune synapses.
Xu Y, Zhang K, Miao J … +7 more , Guo N, Fu X, Yang F, Luo X, Jia J, Zheng Z, Zhu P
Cell Immunol · 2024 · PMID 38909549 · Publisher ↗
CD147 is a T cell activation-associated molecule which is closely involved in the formation of the immune synapse (IS). However, the precise role of CD147 in T cell activation and IS formation remains unclear. In the pre...
CD147 is a T cell activation-associated molecule which is closely involved in the formation of the immune synapse (IS). However, the precise role of CD147 in T cell activation and IS formation remains unclear. In the present study, we demonstrated that CD147 translocated to the IS upon T cell activation and was primarily distributed in the peripheral super molecular cluster (p-SMAC). The knock down of CD147 expression in T cells, but not in B cells, impaired IS formation. CD147 participated in IS formation between T cells and different types of antigen-presenting cells (APCs), including macrophages and dendritic cells. Ligation of CD147 with its monoclonal antibody (mAb) HAb18 effectively inhibited T cell activation and IL-2 secretion. CD98, a critical molecule interacting with CD147, was distributed in IS in a CD147-dependent way. Phosphorylation levels of T cell receptor (TCR) related molecules, like ZAP-70, ERK, and cJun, were down-regulated by CD147 ligation, which is crucial for the interaction of CD147 and TCR signaling transduction. CD147 is indispensable for the formation of immune synapses and plays an important role in the regulation of its function.
Rac1 plays a crucial role in MCP-1-induced monocyte adhesion and migration.
Datta C, Das P, Swaroop S … +1 more , Bhattacharjee A
Cell Immunol · 2024 · PMID 38905771 · Publisher ↗
Monocyte migration is an important process in inflammation and atherogenesis. Identification of the key signalling pathways that regulate monocyte migration can provide prospective targets for prophylactic treatments in...
Monocyte migration is an important process in inflammation and atherogenesis. Identification of the key signalling pathways that regulate monocyte migration can provide prospective targets for prophylactic treatments in inflammatory diseases. Previous research showed that the focal adhesion kinase Pyk2, Src kinase and MAP kinases play an important role in MCP-1-induced monocyte migration. In this study, we demonstrate that MCP-1 induces iPLA activity, which is regulated by PKCβ and affects downstream activation of Rac1 and Pyk2. Rac1 interacts directly with iPLA and Pyk2, and plays a crucial role in MCP-1-mediated monocyte migration by modulating downstream Pyk2 and p38 MAPK activation. Furthermore, Rac1 is necessary for cell spreading and F-actin polymerization during monocyte adhesion to fibronectin. Finally, we provide evidence that Rac1 controls the secretion of inflammatory mediator vimentin from MCP-1-stimulated monocytes. Altogether, this study demonstrates that the PKCβ/iPLA/Rac1/Pyk2/p38 MAPK signalling cascade is essential for MCP-1-induced monocyte adhesion and migration.
Peyer's Patch: Possible target for modulating the Gut-Brain-Axis through microbiota.
Asgari R, Bazzazan MA, Karimi Jirandehi A … +3 more , Yousefzadeh S, Alaei M, Keshavarz Shahbaz S
Cell Immunol · 2024 · PMID 38901288 · Publisher ↗
The gastrointestinal (GI) tract and the brain form bidirectional nervous, immune, and endocrine communications known as the gut-brain axis. Several factors can affect this axis; among them, various studies have focused o...
The gastrointestinal (GI) tract and the brain form bidirectional nervous, immune, and endocrine communications known as the gut-brain axis. Several factors can affect this axis; among them, various studies have focused on the microbiota and imply that alterations in microbiota combinations can influence both the brain and GI. Also, many studies have shown that the immune system has a vital role in varying gut microbiota combinations. In the current paper, we will review the multidirectional effects of gut microbiota, immune system, and nervous system on each other. Specifically, this review mainly focuses on the impact of Peyer's patches as a critical component of the gut immune system on the gut-brain axis through affecting the gut's microbial composition. In this way, some factors were discussed as proposed elements of missing gaps in this field.
Immunological characteristics of CD103CD161 T lymphocytes on chronic rhinosinusitis with nasal polyps.
Sun D, Wang K, Chen Y … +5 more , Zhang B, Tang J, Luo W, Liu J, Yu S
Cell Immunol · 2024 · PMID 38897020 · Publisher ↗
Chronic rhinosinusitis with nasal polyps (CRSwNPs) is a heterogeneous disease characterized by local inflammation of the upper airway and sinus mucosa. T cell-mediated immune responses play irreplaceable roles in the pat...
Chronic rhinosinusitis with nasal polyps (CRSwNPs) is a heterogeneous disease characterized by local inflammation of the upper airway and sinus mucosa. T cell-mediated immune responses play irreplaceable roles in the pathogenesis of nasal polyps. CD161 T cells have been implicated in the pathology of several diseases through cytokine production and cytotoxic activity. However, the immunological characteristics of CD161 T cells in nasal mucosa are still not well understood, particularly in CRSwNPs. Our research revealed a notable enrichment of CD161 T cells in nasal tissues compared to peripheral blood, with a significantly more infiltration of CD161 T cells in CRSwNPs compared to control nasal samples. Phenotypical analysis found that CD161 T cells predominantly co-expressed tissue-resident memory surface markers CD103, CD69, and CD45RO. CD161CD103 T cells demonstrated complicated effector functions, marked by elevated levels of PD-1, CTLA-4, IL-17, and IFN-γ and diminished expression of FoxP3 and CD25. Interestingly, despite CD161 T cells was more abundant in polyp tissues compared to normal control tissues, and then further categorizing polyp samples into distinct groups based on clinical characteristics, only the recurrent CRSwNP group showed a significant reduction in CD161CD8 T cells compared to the primary CRSwNP group. This finding suggested the necessity for further research to comprehensively understand the underlying mechanisms and the broader significance of CD161 T cells in the advancement and relapse of CRSwNPs.
Nasal mucosa-derived mesenchymal stem cells prolonged the survival of septic rats by protecting macrophages from pyroptosis.
Zhang L, Wang Z, Sun X … +5 more , Rong W, Deng W, Yu J, Xu X, Yu Q
Cell Immunol · 2024 · PMID 38880071 · Publisher ↗
Sepsis is characterized by an exacerbated inflammatory response, driven by the overproduction of cytokines, a phenomenon known as a cytokine storm. This condition is further compounded by the extensive infiltration of M1...
Sepsis is characterized by an exacerbated inflammatory response, driven by the overproduction of cytokines, a phenomenon known as a cytokine storm. This condition is further compounded by the extensive infiltration of M1 macrophages and the pyroptosis of these cells, leading to immune paralysis. To counteract this, we sought to transition M1 macrophages into the M2 phenotype and safeguard them from pyroptosis. For this purpose, we employed ectodermal mesenchymal stem cells (EMSCs) sourced from the nasal mucosa to examine their impact on both macrophages and septic animal models. The co-culture protocol involving LPS-stimulated rat bone marrow macrophages and EMSCs was employed to examine the paracrine influence of EMSCs on macrophages. The intravenous administration of EMSCs was utilized to observe the enhancement in the survival rate of septic rat models and the protection of associated organs. The findings indicated that EMSCs facilitated M2 polarization of macrophages, which were stimulated by LPS, and significantly diminished levels of pro-inflammatory cytokines and NLRP3. Furthermore, EMSCs notably restored the mitochondrial membrane potential (MMP) of macrophages through paracrine action, eliminated excess reactive oxygen species (ROS), and inhibited macrophage pyroptosis. Additionally, the systemic integration of EMSCs substantially reduced injuries to multiple organs and preserved the fundamental functions of the heart, liver, and kidney in CLP rats, thereby extending their survival.
Extra-pulmonary control of respiratory defense.
Korkmaz FT, Quinton LJ
Cell Immunol · 2024 · PMID 38878619 · Full text
Pneumonia persists as a public health crisis, representing the leading cause of death due to infection. Whether respiratory tract infections progress to pneumonia and its sequelae such as acute respiratory distress syndr...
Pneumonia persists as a public health crisis, representing the leading cause of death due to infection. Whether respiratory tract infections progress to pneumonia and its sequelae such as acute respiratory distress syndrome and sepsis depends on numerous underlying conditions related to both the causative agent and host. Regarding the former, pneumonia burden remains staggeringly high, despite the effectiveness of pathogen-targeting strategies such as vaccines and antibiotics. This demands a greater understanding of host features that collaborate to promote immune resistance and tissue resilience in the infected lung. Such features inside the pulmonary compartment have drawn much attention, where major advances have been made related to resident and recruited immune activity. By comparison, extra-pulmonary processes guiding pneumonia susceptibility are relatively elusive, constituting the focus of this review. Here we will highlight examples of when, how, and why tissues outside of the lungs dispatch signals that modulate local immunity in the airspaces. Topics include the liver, gut, bone marrow, brain and more, all of which contribute in direct and indirect ways to pneumonia outcome. When tuned appropriately, it has become clear that these responses can serve protective roles, and this will be considered distinctly from what would otherwise be aberrant responses characteristic of pneumonia-induced organ injury and sepsis. Further advances in this area may reveal novel targetable areas for clinical intervention that are not confined to the intra-pulmonary space.
Dopamine β-hydroxylase shapes intestinal inflammation through modulating T cell activation.
Sun Q, Li H, Lv J … +4 more , Shi W, Bai Y, Pan K, Chen A
Cell Immunol · 2024 · PMID 38850753 · Publisher ↗
BACKGROUND: Inflammatory bowel disease (IBD) is a chronic and relapsing disease characterized by immune-mediated dysfunction of intestinal homeostasis. Alteration of the enteric nervous system and the subsequent neuro-im...
BACKGROUND: Inflammatory bowel disease (IBD) is a chronic and relapsing disease characterized by immune-mediated dysfunction of intestinal homeostasis. Alteration of the enteric nervous system and the subsequent neuro-immune interaction are thought to contribute to the initiation and progression of IBD. However, the role of dopamine beta-hydroxylase (DBH), an enzyme converting dopamine into norepinephrine, in modulating intestinal inflammation is not well defined. METHODS: CD4CD45RBT cell adoptive transfer, and 2,4-dinitrobenzene sulfonic acid (DNBS) or dextran sodium sulfate (DSS)-induced colitis were collectively conducted to uncover the effects of DBH inhibition by nepicastat, a DBH inhibitor, in mucosal ulceration, disease severity, and T cell function. RESULTS: Inhibition of DBH by nepicastat triggered therapeutic effects on T cell adoptive transfer induced chronic mouse colitis model, which was consistent with the gene expression of DBH in multiple cell populations including T cells. Furthermore, DBH inhibition dramatically ameliorated the disease activity and colon shortening in chemically induced acute and chronic IBD models, as evidenced by morphological and histological examinations. The reshaped systemic inflammatory status was largely associated with decreased pro-inflammatory mediators, such as TNF-α, IL-6 and IFN-γ in plasma and re-balanced Th1, Th17 and Tregs in mesenteric lymph nodes (MLNs) upon colitis progression. Additionally, the conversion from dopamine (DA) to norepinephrine (NE) was inhibited resulting in increase in DA level and decrease in NE level and DA/NE showed immune-modulatory effects on the activation of immune cells. CONCLUSION: Modulation of neurotransmitter levels via inhibition of DBH exerted protective effects on progression of murine colitis by modulating the neuro-immune axis. These findings suggested a promising new therapeutic strategy for attenuating intestinal inflammation.
Unlocking the power of Zc3h12c: Orchestrating Macrophage activation and elevating the innate immune response.
Zhao Y, Zhu M, Wu S … +9 more , Ou M, Xi Y, Liu Z, Hu R, Li X, Xu T, Xiang X, Zhou Y, Li S
Cell Immunol · 2024 · PMID 38810592 · Publisher ↗
The activation of macrophages, essential for the innate defense against invading pathogens, revolves around Toll-like receptors (TLRs). Nevertheless, a comprehensive understanding of the molecular mechanisms governing TL...
The activation of macrophages, essential for the innate defense against invading pathogens, revolves around Toll-like receptors (TLRs). Nevertheless, a comprehensive understanding of the molecular mechanisms governing TLR signaling in the course of macrophage activation remains to be fully clarified. Although Zc3h12c was originally identified as being enriched in organs associated with macrophages, its precise function remains elusive. In this study, we observed a significant induction of Zc3h12c in macrophages following stimulation with TLR agonists and pathogens. Overexpression of Zc3h12c significantly mitigated the release of TNF-α and IL-6 triggered by lipopolysaccharide (LPS), whereas depletion of Zc3h12c increased the production of the cytokines mentioned above. Notably, the expression of IFN-β was not influenced by Zc3h12c. Luciferase reporter assays revealed that Zc3h12c could suppress the TNF-α promoter activity. Moreover, Zc3h12c exerted a notable inhibitory effect on JNK, ERK, p38, and NF-κB signaling induced by LPS. In summary, the findings of our study suggest that Zc3h12c functions as a robust suppressor of innate immunity, potentially playing a role in the pathogenesis of infectious diseases.
Oridonin attenuates liver ischemia-reperfusion injury by suppressing PKM2/NLRP3-mediated macrophage pyroptosis.
Wu XY, Zhao MJ, Liao W … +5 more , Liu T, Liu JY, Gong JH, Lai X, Xu XS
Cell Immunol · 2024 · PMID 38810591 · Publisher ↗
BACKGROUND: The NOD-like receptor protein 3 (NLRP3) mediated pyroptosis of macrophages is closely associated with liver ischemia reperfusion injury (IRI). As a covalent inhibitor of NLRP3, Oridonin (Ori), has strong anti...
BACKGROUND: The NOD-like receptor protein 3 (NLRP3) mediated pyroptosis of macrophages is closely associated with liver ischemia reperfusion injury (IRI). As a covalent inhibitor of NLRP3, Oridonin (Ori), has strong anti-inflammasome effect, but its effect and mechanisms for liver IRI are still unknown. METHODS: Mice and liver macrophages were treated with Ori, respectively. Co-IP and LC-MS/MS analysis of the interaction between PKM2 and NLRP3 in macrophages. Liver damage was detected using H&E staining. Pyroptosis was detected by WB, TEM, and ELISA. RESULTS: Ori ameliorated liver macrophage pyroptosis and liver IRI. Mechanistically, Ori inhibited the interaction between pyruvate kinase M2 isoform (PKM2) and NLRP3 in hypoxia/reoxygenation（H/R）-induced macrophages, while the inhibition of PKM2/NLRP3 reduced liver macrophage pyroptosis and liver IRI. CONCLUSION: Ori exerted protective effects on liver IRI via suppressing PKM2/NLRP3-mediated liver macrophage pyroptosis, which might become a potential therapeutic target in the clinic.
Triptolide promotes differentiation of human monocytes into immunosuppressive MDSCs.
Wang H, Yang H, Zhang X … +1 more , Zhou X
Cell Immunol · 2024 · PMID 38776753 · Publisher ↗
BACKGROUND: Myeloid-derived suppressor cells (MDSCs) negatively modulate immune activity. Prior investigations have shown much promise in using MDSCs-assisted immunotherapy for organ transplantation patients. Additionall...
BACKGROUND: Myeloid-derived suppressor cells (MDSCs) negatively modulate immune activity. Prior investigations have shown much promise in using MDSCs-assisted immunotherapy for organ transplantation patients. Additionally, owing to its immunosuppressive activity, MDSCs can also be used to manage immune-associated disorders. METHODS: Granulocyte-macrophage colony-stimulating factor (GM-CSF) was employed to stimulate myeloid progenitor cell differentiation. Triptolide (PG490) was introduced toward the later phases of in vitro MDSCs induction. Lastly, real-time PCR (RT-PCR) and flow cytometry were used to assess transcript expression and cell phenotype, and a mouse skin transplantation model was established to evaluate the MDSCs-mediated immune suppression in vivo. RESULTS: Co-stimulation with PG490 and GM-CSF potently induced myeloid-derived monocytes to form MDSCs, with remarkable immune-suppressive activity. The underlying mechanism involved downregulation of T cell proliferation, activation, enhancement of inflammatory cytokine release, as well as T cell conversion to Treg cells. PG490 strongly enhanced iNOS expression in MDSCs, and iNOS inhibition successfully reversed the immune-suppression. The PG490- and GM-CSF-induced MDSCs substantially extended survival duration of murine skin grafts, thereby validating their strong immune-suppressive activity in vivo. CONCLUSIONS: Herein, we presented a new approach involving MDSCs-based immunosuppression in vitro. PG490 and GM-CSF co-treatment strongly induced immuno-suppressive activity in MDSCs both in vitro and in vivo. Our findings highlight the promise of applying MDSCs-based therapy in clinical organ transplantation treatment.
Group2 innate lymphoid cells ameliorate renal fibrosis and dysfunction associated with adenine-induced CKD.
Nagashima R, Ishikawa H, Kuno Y … +3 more , Kohda C, Eshima K, Iyoda M
Cell Immunol · 2024 · PMID 38759328 · Publisher ↗
Renal fibrosis is a common pathway of chronic kidney disease (CKD) progression involving primary kidney injury and kidney diseases. Group 2 innate lymphoid cells (ILC2s) mediate type 2 immune responses irrespective of an...
Renal fibrosis is a common pathway of chronic kidney disease (CKD) progression involving primary kidney injury and kidney diseases. Group 2 innate lymphoid cells (ILC2s) mediate type 2 immune responses irrespective of antigen presentation and play a reno-protective role in kidney injury and disease. In the present study, we observed a decrease in kidney-resident ILC2s in CKD and found that enrichment of ILC2s in the kidney ameliorates renal fibrosis. In CKD kidney, ILC2s preferentially produced IL-13 over IL-5 in response to IL-33 stimulation, regardless of ST2L expression. Moreover, GATA3 expression was decreased in ILC2s, and T-bet+ ILC1s and RORγt+ ILC3s were increased in CKD kidney. Adoptive transfer of kidney ILC2s into adenine-induced CKD model mouse improved renal function and fibrosis. Renal fibroblasts cultured with IL33-activated kidney ILC2s suppressed myofibroblast trans-differentiation through Acta2 and Fn-1 regulation. These results suggest that kidney ILC2s prevent CKD progression via improvement of renal fibrosis. Our findings also suggest that ILC2s may contribute to the development of new therapeutic agents and strategies for tissue fibroses.
Characterization of the immune suppressive functions of eosinophils.
Qing B, Li M, Peng D … +5 more , Wang J, Song S, Mo L, Li G, Yang P
Cell Immunol · 2024 · PMID 38754338 · Publisher ↗
Eosinophils account for a significant portion of immune cells in the body. It is well known that eosinophils play a role in the pathogenesis of many diseases. In which the interaction between eosinophils and other immune...
Eosinophils account for a significant portion of immune cells in the body. It is well known that eosinophils play a role in the pathogenesis of many diseases. In which the interaction between eosinophils and other immune cells is incompletely understood. The aim of this study is to characterize the immune suppressive functions of eosinophils. In this study, an irway allergy mouse model was established. Eosinophils were isolated from the airway tissues using flow cytometry cell sorting. The RAW264.7 cell line was used to test the immune suppressive functions of eosinophils. We observed that eosinophils had immune suppressive functions manifesting inhibiting immune cell proliferation and cytokine release from other immune cells. The eosinophil's immune suppressive functions were mediated by eosinophil-derived molecules, such as eosinophil peroxidase (EPX) and major basic protein (MBP). The expression of Ras-like protein in the brain 27a (Rab27a) was detected in eosinophils, which controlled the release of MBP and EPX by eosinophils. Eosinophil mediators had two contrast effects on inducing inflammatory responses or rendering immune suppressive effects, depending on the released amounts. Administration of an inhibitor of Rab27a at proper dosage could alleviate experimental airway allergy. To sum up, eosinophils have immune suppressive functions and are also inflammation inducers. Rab27a governs the release of EPX and MBP from eosinophils, which leads to immune suppression or inflammation. Modulation of Rab27a can alleviate airway allergy responses by modulating eosinophil's immune suppressive functions, which has the translational potential for the management of eosinophil-related diseases.
Enhancing antitumor response by efficiently generating large-scale TCR-T cells targeting a single epitope across multiple cancer antigens.
Amissah OB, Basnet R, Chen W … +5 more , Habimana JD, Baiden BE, Owusu OA, Saeed BJ, Li Z
Cell Immunol · 2024 · PMID 38733699 · Publisher ↗
The need to contrive interventions to curb the rise in cancer incidence and mortality is critical for improving patients' prognoses. Adoptive cell therapy is challenged with quality large-scale production, heightening it...
The need to contrive interventions to curb the rise in cancer incidence and mortality is critical for improving patients' prognoses. Adoptive cell therapy is challenged with quality large-scale production, heightening its production cost. Several cancer types have been associated with the expression of highly-immunogenic CTAG1 and CTAG2 antigens, which share common epitopes. Targeting two antigens on the same cancer could improve the antitumor response of TCR-T cells. In this study, we exploited an efficient way to generate large-fold quality TCR-T cells and also demonstrated that the common epitopes of CTAG1 and CTAG2 antigens provide an avenue for improved cancer-killing via dual-antigen-epitope targeting. Our study revealed that xeno/sera-free medium could expand TCR-T cells to over 500-fold, posing as a better replacement for FBS-supplemented media. Human AB serum was also shown to be a good alternative in the absence of xeno/sera-free media. Furthermore, TCR-T cells stimulated with beads-coated T-activator showed a better effector function than soluble T-activator stimulated TCR-T cells. Additionally, TCR-T cells that target multiple antigens in the same cancer yield better anticancer activity than those targeting a single antigen. This showed that targeting multiple antigens with a common epitope may enhance the antitumor response efficacy of T cell therapies.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe