Cellular immunology最新文献_第3页

Complement system component 3 deficiency modulates the phenotypic profile of murine macrophages 补体系统成分 3 缺乏可调节小鼠巨噬细胞的表型特征

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-10-22 DOI: 10.1016/j.cellimm.2024.104886

Tiago Francisco da Silva , Thaís Akemi Amamura , Iuri Cordeiro Valadão , Milena Carvalho Carneiro , Vanessa Morais Freitas , Ana Paula Lepique , Lourdes Isaac

{"title":"Complement system component 3 deficiency modulates the phenotypic profile of murine macrophages","authors":"Tiago Francisco da Silva , Thaís Akemi Amamura , Iuri Cordeiro Valadão , Milena Carvalho Carneiro , Vanessa Morais Freitas , Ana Paula Lepique , Lourdes Isaac","doi":"10.1016/j.cellimm.2024.104886","DOIUrl":"10.1016/j.cellimm.2024.104886","url":null,"abstract":"<div><div>The Complement System is composed of more than 40 proteins that act in innate and adaptive immunity. C3 is the most abundant one and C3-deficient patients are more susceptible to recurrent and severe infections. Several studies have demonstrated the importance of C3 in controlling infections. However, its role in leukocyte biology is still poorly understood. This study aimed to evaluate several cellular parameters in macrophages from C3-deficient mice and compare them to similar cells from wild-type counterparts. We observed that in the absence of C3, the population of F4/80<sup>low</sup> macrophages in the peritoneal cavity of thioglycolate-treated mice is diminished, probably due to the lack of chemotactic factors like C3a and low levels of C5a. Using fluorescence microscopy analysis, we observed that macrophages from C3-deficient mice exhibited morphological alterations when compared to similar cells from wild-type mice. We observed a significant increase in the expression of CD11c, which is part of CR4 (CD11c/CD18), in macrophages from C3-deficient compared to cells from wild-type mice. Treatment with 12-<em>o</em>-tetradecanoylphorbol-13-acetate, stimulated ROS production and MAPK activation by macrophages. However, these parameters were lower in macrophages from C3-deficient mice when compared to wild-type counterparts. In addition, the phagocytosis of iC3b-opsonized Zymosan particles was diminished in macrophages from C3-deficient mice. Our results suggest that C3 deficiency in C57Black/6 mice may influence specific morphological and functional parameters of macrophages, cells of fundamental importance for both the innate and acquired immune responses.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"405 ","pages":"Article 104886"},"PeriodicalIF":3.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IL-10: A Key Regulator and potential therapeutic target in uveitis IL-10：葡萄膜炎的关键调节因子和潜在治疗靶点。

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-10-18 DOI: 10.1016/j.cellimm.2024.104885

Chengzhi Liu, Xinyu Wang, Xusheng Cao

{"title":"IL-10: A Key Regulator and potential therapeutic target in uveitis","authors":"Chengzhi Liu, Xinyu Wang, Xusheng Cao","doi":"10.1016/j.cellimm.2024.104885","DOIUrl":"10.1016/j.cellimm.2024.104885","url":null,"abstract":"<div><div>Uveitis is a prevalent inflammatory eye disease that primarily affects working-age individuals and can lead to blindness if untreated. Interleukin-10 (IL-10) is a multifunctional cytokine with broad immunosuppressive properties and plays a significant role in various pathological and physiological processes. However, its specific role and underlying mechanisms in uveitis remain incompletely understood. This review aims to shed light on the biological characteristics of IL-10, its involvement in the uveitis pathophysiology, and its potential as a novel therapeutic target. By examining existing literature, the review analyzes IL-10 expression levels and regulatory mechanisms in different types of uveitis, discussing its role in immune regulation. Despite IL-10 being expressed variably across various forms of autoimmune uveitis, studies consistently highlight its protective role, prompting research into ways to enhance its bioavailability in the eye. IL-10 is often upregulated in infectious uveitis, contributing to pathogen immune evasion. Furthermore, primary intraocular lymphoma (PIOL), which shares clinical similarities with uveitis, also shows upregulated IL-10 levels, whereas IL-6 is more commonly elevated in uveitis. This differential expression suggests that IL-6 and IL-10 could be diagnostic markers to distinguish between PIOL and uveitis. Future research should continue to focus on elucidating the molecular mechanisms of IL-10 in uveitis, exploring its potential therapeutic applications, and developing targeted treatments that leverage the immunomodulatory effects of IL-10 to prevent and manage this sight-threatening condition.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"405 ","pages":"Article 104885"},"PeriodicalIF":3.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

House dust mite allergen directly activates ILC2 cells via the TLR4 signaling pathway in allergic airway diseases 在过敏性气道疾病中，屋尘螨过敏原通过 TLR4 信号通路直接激活 ILC2 细胞。

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-10-18 DOI: 10.1016/j.cellimm.2024.104884

Yan Li , Zhennan Qu , Xue Wang , Qiqi Wang , Zhe Lv , Wei Wang , Sun Ying , Luo Zhang , Feng Lan

{"title":"House dust mite allergen directly activates ILC2 cells via the TLR4 signaling pathway in allergic airway diseases","authors":"Yan Li , Zhennan Qu , Xue Wang , Qiqi Wang , Zhe Lv , Wei Wang , Sun Ying , Luo Zhang , Feng Lan","doi":"10.1016/j.cellimm.2024.104884","DOIUrl":"10.1016/j.cellimm.2024.104884","url":null,"abstract":"<div><h3>Background</h3><div>Unlike T cells and B cells, the activation process of group 2 innate lymphoid cells (ILC2s) is mainly driven by epithelial cell derived cytokines rather than specific antigen recognition. Whether antigens have a direct role in activating ILC2s remains poorly understood.</div></div><div><h3>Methods</h3><div>Following stimulation, type 2 cytokine secretions and cell death were assessed in house dust mite (HDM)-stimulated ILC2s. To investigate the underlying mechanisms, RNA-sequencing (RNA-seq) was performed on HDM-stimulated ILC2s. The validation experiments were done through <em>in vitro</em> stimulation assays and an HDM-induced asthmatic murine model, using specific inhibitors targeting receptor and relevant proteins of signaling pathways.</div></div><div><h3>Results</h3><div>HDM stimulation increased the secretion of IL-5 and IL-13 cytokines from ILC2s, inhibited apoptosis of ILC2, and promoted the proliferation of ILC2s. As confirmed by RNA-seq, HDM stimulation upregulated genes in ILC2s, including those responsible for type 2 cytokines, ILC2s-specific transcriptional factors, and related receptors. Both toll-like receptor (TLR) 1 and TLR4 were constitutively expressed on ILC2s, however, only TLR4 was predominantly upregulated upon HDM stimulation. TAK242, a specific TLR4 inhibitor, significantly blocked the effect of HDM on ILC2s, in terms of type 2 cytokine secretions and cell death. Using specific inhibitors in pathways, we confirmed that HDM promoted ILC2s activation via TLR4-ERK, p38, and NF-κB signaling pathways.</div></div><div><h3>Conclusions</h3><div>Allergen HDM directly activates ILC2s through TLR4 mediated-ERK/p38/NF-κB signaling pathway. These findings provide new insights into how antigens propagate type 2 immune response via ILC2s, contributing to chronic inflammations in allergic airway diseases.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"405 ","pages":"Article 104884"},"PeriodicalIF":3.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

B cell-intrinsic IFN-γ promotes excessive CD11c+ age-associated B cell differentiation and compromised germinal center selection in lupus mice 狼疮小鼠体内的 B 细胞内源性 IFN-γ 促进了 CD11c+ 年龄相关 B 细胞的过度分化，并损害了生殖中心的选择能力

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-10-18 DOI: 10.1016/j.cellimm.2024.104883

Shujun Liu , Wenqian Zhang , Shihao Tian , Yan Zhang , Zhinan Yin , Gonghua Huang , Huihui Zhang , Fubin Li

{"title":"B cell-intrinsic IFN-γ promotes excessive CD11c+ age-associated B cell differentiation and compromised germinal center selection in lupus mice","authors":"Shujun Liu , Wenqian Zhang , Shihao Tian , Yan Zhang , Zhinan Yin , Gonghua Huang , Huihui Zhang , Fubin Li","doi":"10.1016/j.cellimm.2024.104883","DOIUrl":"10.1016/j.cellimm.2024.104883","url":null,"abstract":"<div><div>CD11c<sup>+</sup> age-associated B cells (ABCs) have emerged as a key component in protective and autoreactive B cell responses. Lupus is an autoimmune disorder linked to reduced efficacy of vaccines and increased susceptibility to infections. Previously, we reported that excessive CD11c<sup>+</sup> ABCs not only significantly contribute to autoantibody production but also promote aberrant T cell activation and compromised affinity-based germinal center selection in response to immunization in lupus mice. Yet, the regulation of CD11c<sup>+</sup> ABC differentiation is not fully understood. In this study, we show that B cell-intrinsic IFN-γ is required for excessive CD11c<sup>+</sup> ABC differentiation in lupus mice. B cell-intrinsic IFN-γ is mainly produced by CD11c<sup>+</sup> ABCs. IFN-γ-deficiency leads to decreased expression of ABC characteristic genes. We further show that ablating IFN-γ can normalize T cell overactivation and rescue antigen-specific GC responses in lupus mice. Our study offers insight into the crucial role of B cell-intrinsic IFN-γ in promoting excessive CD11c<sup>+</sup> ABC differentiation, which compromises affinity-based germinal center selection and affinity maturation in lupus, providing a potential strategy to normalize vaccine responses in lupus.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"405 ","pages":"Article 104883"},"PeriodicalIF":3.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unveiling the impact of TREM-2+ Macrophages in metabolic disorders 揭示 TREM-2+ 巨噬细胞在代谢紊乱中的影响。

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-10-04 DOI: 10.1016/j.cellimm.2024.104882

Mike Telemaco Contreras Colmenares, Amanda de Oliveira Matos, Pedro Henrique dos Santos Dantas, José Rodrigues do Carmo Neto, Marcelle Silva-Sales, Helioswilton Sales-Campos

{"title":"Unveiling the impact of TREM-2+ Macrophages in metabolic disorders","authors":"Mike Telemaco Contreras Colmenares, Amanda de Oliveira Matos, Pedro Henrique dos Santos Dantas, José Rodrigues do Carmo Neto, Marcelle Silva-Sales, Helioswilton Sales-Campos","doi":"10.1016/j.cellimm.2024.104882","DOIUrl":"10.1016/j.cellimm.2024.104882","url":null,"abstract":"<div><div>The Triggering Receptor Expressed on Myeloid cells 2 (TREM-2) has been widely known by its anti-inflammatory activity. It can be activated in response to microbes and tissue damage, leading to phagocytosis, autophagy, cell polarization and migration, counter inflammation, and tissue repair. So far, the receptor has been largely explored in neurodegenerative disorders, however, a growing number of studies have been investigating its contribution in different pathological conditions, including metabolic diseases, in which (resident) macrophages play a crucial role. In this regard, TREM-2 + macrophages have been implicated in the onset and development of obesity, atherosclerosis, and fibrotic liver disease. These macrophages can be detected in the brain, white adipose tissue, liver, and vascular endothelium. In this review we discuss how different murine models have been demonstrating the ability of such cells to contribute to tissue and body homeostasis by phagocytosing cellular debris and lipid structures, besides contributing to lipid homeostasis in metabolic diseases. Therefore, understanding the role of TREM-2 in metabolic disorders is crucial to expand our current knowledge concerning their immunopathology as well as to foster the development of more targeted therapies to treat such conditions.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"405 ","pages":"Article 104882"},"PeriodicalIF":3.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Netosis and trained immunity in tick-borne diseases: a possible pathogenetic role 蜱传疾病中的净毒和训练有素的免疫力：可能的致病作用。

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-10-02 DOI: 10.1016/j.cellimm.2024.104881

Giusto Davide Badami , Bartolo Tamburini , Leila Mohammadnezhad , Rita Vaz-Rodrigues , Lidia La Barbera , José de la Fuente , Guido Sireci

{"title":"Netosis and trained immunity in tick-borne diseases: a possible pathogenetic role","authors":"Giusto Davide Badami , Bartolo Tamburini , Leila Mohammadnezhad , Rita Vaz-Rodrigues , Lidia La Barbera , José de la Fuente , Guido Sireci","doi":"10.1016/j.cellimm.2024.104881","DOIUrl":"10.1016/j.cellimm.2024.104881","url":null,"abstract":"<div><div>Various types of pathogens transmitted by ticks elicit distinct immune responses just like the emerging α-Gal syndrome that is associated with allergic reactions to tick bites. The mechanisms of Neutrophil Extracellular Traps release (called NETosis) and trained immunity in response to tick-borne microbes have not been extensively investigated. In our paper, we explored the intricate interplay of NETosis and trained immunity within the realm of infectious diseases triggered by tick bites and their possible pathogenetic role in autoimmunity. We conducted an extensive literature search to identify studies for this review, considering articles and reviews published in English within the last years. Additionally, we scrutinized the references of all included papers and relevant review articles to ensure comprehensive coverage. We shed light on a plausible correlation between these innate immune responses and their potential implication in certain pathological conditions, with a specific focus on some autoimmune diseases. These findings offer new perspectives for a more profound comprehension of the immunopathogenesis of certain autoimmune-like signs where clinicians should include Tick-Borne Diseases (TBDs) in their differential diagnoses, in those geographical areas of tick infestation.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"405 ","pages":"Article 104881"},"PeriodicalIF":3.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation of TNF-α and IFN-γ primed conditioned medium of mesenchymal stem cell in acetic acid-induced mouse model of acute colitis 间充质干细胞TNF-α和IFN-γ条件培养基在醋酸诱导的急性结肠炎小鼠模型中的应用评估

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-09-24 DOI: 10.1016/j.cellimm.2024.104876

Manizhe Faghih , Mona Moshiri , Nader Mazrouei Arani , Fatemeh Ahmadzadeh , Narjes Jafari , Maryam Ghasemi , Saeid Abediankenari

{"title":"Evaluation of TNF-α and IFN-γ primed conditioned medium of mesenchymal stem cell in acetic acid-induced mouse model of acute colitis","authors":"Manizhe Faghih , Mona Moshiri , Nader Mazrouei Arani , Fatemeh Ahmadzadeh , Narjes Jafari , Maryam Ghasemi , Saeid Abediankenari","doi":"10.1016/j.cellimm.2024.104876","DOIUrl":"10.1016/j.cellimm.2024.104876","url":null,"abstract":"<div><div>IBD, an autoimmune-inflammatory disorder that affects people who are genetically prone to inflammation. There is a lot of interest in MSC-CM therapy, especially when primed with TNF-α + IFN-γ. Throughout the study, data were collected on the percentage of apoptotic cells, gene expression of ZO-1, Foxp3, GATA3, IDO-1, Muc2, <em>T</em>-bet, Notch1, TNFR2, and ROR-γt, colon weight and length, histopathological analysis, and DAI. TNF-α and IL-10 levels were assessed in addition to the NO level. The results suggest that primed MSC-CM improved DAI, mucosal deterioration, intestinal inflammation and NO concentration. The amount of TNF-α was decreased, but IL-10 and the colon’s percentage of apoptotic cells was increased. The mRNA expression of ZO-1, Foxp3, GATA3, IDO-1, and Muc2 genes increased greatly in the treatment groups, while the expression of <em>T</em>-bet, Notch1, TNFR2, and ROR-γt genes has decreased. These studies suggest that primed MSC-CM may combine with common treatments to improve responsiveness.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"405 ","pages":"Article 104876"},"PeriodicalIF":3.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Embracing multiple infection models to tackle Q fever: A review of in vitro, in vivo, and lung ex vivo models 采用多种感染模型应对 Q 热：体外、体内和肺部体外模型综述。

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-09-24 DOI: 10.1016/j.cellimm.2024.104880

R. Marena Guzman, Daniel E. Voth

{"title":"Embracing multiple infection models to tackle Q fever: A review of in vitro, in vivo, and lung ex vivo models","authors":"R. Marena Guzman, Daniel E. Voth","doi":"10.1016/j.cellimm.2024.104880","DOIUrl":"10.1016/j.cellimm.2024.104880","url":null,"abstract":"<div><div>Multiple animal and cell culture models are employed to study pathogenesis of <em>Coxiella burnetii</em>, the causative agent of acute and chronic human Q fever. <em>C. burnetii</em> is a lung pathogen that is aerosolized in contaminated products and inhaled by humans to cause acute disease that can disseminate to other organs and establish chronic infection. Cellular models of Q fever include a variety of tissue-derived cell lines from mice and humans such as lung alveolar <em>ex vivo</em> cells. These models have the advantage of being cost-effective and reproducible. Similarly, animal models including mice and guinea pigs are cost-effective, although only immunocompromised SCID mice display a severe disease phenotype in response to Nine Mile I and Nine Mile II isolates of <em>C. burnetii</em> while immunocompetent guinea pigs display human-like symptoms and robust immune responses. Non-human primates such as macaques and marmosets are the closest model of human disease but are costly and largely used for adaptive immune response studies. All animal models are used for vaccine development but many differences exist in the pathogen’s ability to establish lung infection when considering infection routes, bacterial isolates, and host genetic background. Similarly, while cellular models are useful for characterization of host-pathogen mechanisms, future developments should include use of a lung infection platform to draw appropriate conclusions. Here, we summarize the current state of the <em>C. burnetii</em> lung pathogenesis field by discussing the contribution of different animal and cell culture models and include suggestions for continuing to move the field forward.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"405 ","pages":"Article 104880"},"PeriodicalIF":3.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neutralization of TLR2 in combination with either TNF-α or IL-1β antibody reduces the severity of septic arthritis through STAT3/mTOR signalling in lymphocytes 中和 TLR2 与 TNF-α 或 IL-1β 抗体相结合，可通过淋巴细胞中的 STAT3/mTOR 信号减轻化脓性关节炎的严重程度。

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-09-18 DOI: 10.1016/j.cellimm.2024.104878

Rituparna Ghosh, Biswadev Bishayi

{"title":"Neutralization of TLR2 in combination with either TNF-α or IL-1β antibody reduces the severity of septic arthritis through STAT3/mTOR signalling in lymphocytes","authors":"Rituparna Ghosh, Biswadev Bishayi","doi":"10.1016/j.cellimm.2024.104878","DOIUrl":"10.1016/j.cellimm.2024.104878","url":null,"abstract":"<div><div><em>Staphylococcus aureus</em> induced Septic arthritis is considered a medical concern. <em>S.aureus</em> binds TLR2 to induce an array of inflammatory responses. Generation of pro-inflammatory cytokines induces T cell responses and control Th17/Treg cell balance. Regulation of T cell-mediated immunity in response to inflammation is significantly influenced by mTOR. Presence of elevated TNF-α, IL-1β decreases Treg cell activity through STAT3/mTOR, promoting proliferation of T cells towards Th17 cells. Therefore, we postulated, neutralizing TLR2 with either TNF-α or IL-1β in combination could be useful in modifying Th17/Treg cell ratio in order to treat septic arthritis by suppressing expression of mTOR/STAT3. To date, no studies have reported effects of neutralization of TLR2 along with either TNF-α or IL-1β on amelioration of arthritis correlating with mTOR/STAT3 expression. Contribution of T lymphocytes collected from blood, spleen, synovial tissues, their derived cytokines IFN-γ, IL-6, IL-17, TGF-β, IL-10 were noted. Expression of TLR2, TNFR1, TNFR2, NF-κB along with mTOR/STAT3 also recorded. Neutralization of TLR2 along with TNF-α and IL-1β were able to shift Th17 cells into immunosuppressive Treg cells. Furthermore,elevated expression of IL-10, TNFR2 and demoted expression of mTOR/ STAT3 along with NF-κB in lymphocytes confirms its role in resolution of arthritis. It was also effective in reducing oxidative stress via increasing expression of the antioxidant enzymes. As a result, it can be inferred that Treg-derived IL-10, which may mitigate inflammatory effects of septic arthritis by influencing the mTOR/STAT3 interaction in lymphocytes, may be selected as a different therapeutic strategy for reducing the impact of septic arthritis.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"405 ","pages":"Article 104878"},"PeriodicalIF":3.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploration of immunomodulatory mechanism of caprine Wharton’s jelly derived mesenchymal stem cells 探索黄羊沃顿果冻间充质干细胞的免疫调节机制

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-09-17 DOI: 10.1016/j.cellimm.2024.104879

Indu Baiju , Mukesh Kumar Bharti , Anjali Somal , Sriti Pandey , Irfan A. Bhat , Anand Joseph , Vikash Chandra , G. Taru Sharma

{"title":"Exploration of immunomodulatory mechanism of caprine Wharton’s jelly derived mesenchymal stem cells","authors":"Indu Baiju , Mukesh Kumar Bharti , Anjali Somal , Sriti Pandey , Irfan A. Bhat , Anand Joseph , Vikash Chandra , G. Taru Sharma","doi":"10.1016/j.cellimm.2024.104879","DOIUrl":"10.1016/j.cellimm.2024.104879","url":null,"abstract":"<div><p>The present study was aimed to explore the possible mechanisms by which caprine Wharton’s jelly-derived MSCs (WJ-MSCs) perform their immunomodulatory function. WJ-MSCs were isolated through explants culture and characterized as per ISCT criteria using culture behavior, expression of surface markers by PCR, FACS and immunocytochemical localization (ICC), trilineage differentiation potential etc. Secretory behavior for important biomolecules (IDO, TGFβ1, VEGF, IL6) was evaluated by ICC and western blot assay. Cell-to-cell communication was studied by culturing cells in cell–cell contact and <em>trans</em>-well system. The MSCs when co-cultured with activated Tc and Th cells, down-regulation of T cell cytokine as well as upregulation of immunomodulatory factors (VEGF A, IL10, IL6, IDO, iNOS, PTGS2, HGF, TGFβ, CXCL10, CXCL11) was noticed in both cell–cell contact and <em>trans</em>-well culture system which was significantly higher in cell–cell contact system. Trilineage differentiation of MSCs showed significant upregulation of MHC I (CAHI) and MHC II (CLA DRB3) molecules suggesting better clinical applications of MSCs without differentiation to avoid immune rejection. It can be concluded that WJ-MSCs perform their immunomodulation through the secretion of a battery of biomolecules and work in both cell–cell contact manner and through their secretome.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"405 ","pages":"Article 104879"},"PeriodicalIF":3.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142272431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0