{"title":"Genetic deficiencies of both IL-4 receptor alpha chain and IL-10 trigger early onset of severe colitis in mice","authors":"Hisashi Nagase , Masaya Takamoto , Nancy Noben-Trauth","doi":"10.1016/j.cellimm.2023.104779","DOIUrl":"10.1016/j.cellimm.2023.104779","url":null,"abstract":"<div><p>Inflammatory bowel diseases are associated with dysregulated inflammatory immune responses in the gastrointestinal tract. We found that deficiencies of both IL-4 receptor alpha chain (IL-4Rα) and IL-10 in BALB/c mice (IL-4Rα × IL-10 KO mice) highly induced spontaneous rectal prolapse and diarrhea. These mice also exhibited severe colitis in their cecum and colon and marked elevation of serum proinflammatory cytokines including TNFα and IFNγ. These pathologies were transmittable with their cecal contents containing <em>Helicobacter</em> spp. Their mesenteric LN cells produced TNFα and IFNγ in response to soluble <em>H. hepaticus</em> antigens and high titers of <em>H. hepaticus</em>-specific serum IgG were also detected. These results suggested the important function of IL-4Rα signaling in controlling the intestinal inflammation and the susceptibility to intestinal microbes including <em>H. hepaticus</em>. Therefore, these IL-4Rα × IL-10 KO mice potentially provide the significant murine model for clarifying the causes and control of spontaneous colitis and intestinal inflammation.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"393 ","pages":"Article 104779"},"PeriodicalIF":4.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71478443","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}
Fangfang Liang , Cheng Peng , Xianze Luo , Linlin Wang , Yanyan Huang , Le Yin , Luming Yue , Jun Yang , Xiaodong Zhao
{"title":"A single-cell atlas of immunocytes in the spleen of a mouse model of Wiskott-Aldrich syndrome","authors":"Fangfang Liang , Cheng Peng , Xianze Luo , Linlin Wang , Yanyan Huang , Le Yin , Luming Yue , Jun Yang , Xiaodong Zhao","doi":"10.1016/j.cellimm.2023.104783","DOIUrl":"10.1016/j.cellimm.2023.104783","url":null,"abstract":"<div><p>Wiskott-Aldrich syndrome (WAS) is a disorder characterized by rare X-linked genetic immune deficiency with mutations in the <em>Was</em> gene, which is specifically expressed in hematopoietic cells. The spleen plays a major role in hematopoiesis and red blood cell clearance. However, to date, comprehensive analyses of the spleen in wild-type (WT) and WASp-deficient (WAS-KO) mice, especially at the transcriptome level, have not been reported. In this study, single-cell RNA sequencing (scRNA-seq) was adopted to identify various types of immune cells and investigate the mechanisms underlying immune deficiency. We identified 30 clusters and 10 major cell subtypes among 11,269 cells; these cell types included B cells, T cells, dendritic cells (DCs), natural killer (NK) cells, monocytes, macrophages, granulocytes, stem cells and erythrocytes. Moreover, we evaluated gene expression differences among cell subtypes, identified differentially expressed genes (DEGs), and performed enrichment analyses to identify the reasons for the dysfunction in these different cell populations in WAS. Furthermore, some key genes were identified based on a comparison of the DEGs in each cell type involved in specific and nonspecific immune responses, and further analysis showed that these key genes were previously undiscovered pathology-related genes in WAS-KO mice. In summary, we present a landscape of immune cells in the spleen of WAS-KO mice based on detailed data obtained at single-cell resolution. These unprecedented data revealed the transcriptional characteristics of specific and nonspecific immune cells, and the key genes were identified, laying a foundation for future studies of WAS, especially studies into novel and underexplored mechanisms that may improve gene therapies for WAS.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"393 ","pages":"Article 104783"},"PeriodicalIF":4.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72013720","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}
Brenal K. Singh , Yuichi Yokoyama , Yukinori Tanaka , Dorottya Laczkó , Deepak A. Deshpande , Taku Kambayashi
{"title":"Diacylglycerol kinase zeta deficiency attenuates papain-induced type 2 airway inflammation","authors":"Brenal K. Singh , Yuichi Yokoyama , Yukinori Tanaka , Dorottya Laczkó , Deepak A. Deshpande , Taku Kambayashi","doi":"10.1016/j.cellimm.2023.104780","DOIUrl":"10.1016/j.cellimm.2023.104780","url":null,"abstract":"<div><p>Allergic airway diseases are caused by inappropriate immune responses directed against inhaled environmental antigens. We previously reported that the inhibition of diacylglycerol (DAG) kinase<!--> <!-->ζ (DGKζ),<!--> <!-->an enzyme that terminates DAG-mediated signaling,<!--> <!-->protects against T cell-mediated allergic airway inflammation by blocking Th2 cell differentiation.<!--> <!-->In this study, we tested whether DGKζ deficiency also affects allergic airway disease mediated by type 2 innate lymphoid cells (ILC2)s. DGKζ-deficient mice displayed diminished ILC2 function and reduced papain-induced airway inflammation compared to wildtype mice. Unexpectedly, however, mice with hematopoietic cell-specific deletion of<!--> <span>DGKζ displayed intact airway inflammation upon papain challenge. Rather, bone marrow chimera studies revealed that</span> <!-->DGKζ deficiency in the non-hematopoietic compartment was responsible for the reduction in papain-induced airway inflammation. These data suggest that DGK might represent a novel therapeutic target not only for T cell-dependent but also ILC2-dependent allergic airway inflammation by affecting non-hematopoietic cells.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"393 ","pages":"Article 104780"},"PeriodicalIF":4.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71421054","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}
Naina Monga , Shikha Sharma , Ruchika Bhatia , Mahendra Bishnoi , Kanthi Kiran Kondepudi , Amarjit S. Naura
{"title":"Immunomodulatory action of synbiotic comprising of newly isolated lactic acid producing bacterial strains against allergic asthma in mice","authors":"Naina Monga , Shikha Sharma , Ruchika Bhatia , Mahendra Bishnoi , Kanthi Kiran Kondepudi , Amarjit S. Naura","doi":"10.1016/j.cellimm.2023.104786","DOIUrl":"10.1016/j.cellimm.2023.104786","url":null,"abstract":"<div><p>Given the reported role of gut-microbiota in asthma pathogenesis, the present work was carried to evaluate immunomodulatory action of newly isolated lactic acid producing bacterial strains <em>Bifidobacterium breve</em> Bif11 and <em>Lactiplantibacillus plantarum</em> LAB31 against asthma using ovalbumin (OVA) based mouse model. Our results show that both strains modulate Th2 immune response potentially through production of short chain fatty acids (SCFAs), resulting in suppression of OVA-induced airway inflammation. Furthermore, synbiotic comprising of both strains and prebiotic, Isomaltooligosaccharide exhibited superior potential in amelioration of OVA-induced airway inflammation through improved modulation of Th2 immune response. Further, synbiotic protects against OVA-induced mucus hyper-production and airway-hyperresponsiveness. Such protection was associated with normalization of gut microbiome and enhanced production of SCFAs in cecum which correlates closely with population of T-regulatory cells in spleen. Overall, our novel synbiotic possesses the ability to fine-tune the immune response for providing protection against allergic asthma.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"393 ","pages":"Article 104786"},"PeriodicalIF":4.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135615316","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}
{"title":"Anti-CD19/CD8 bispecific T cell engager for the potential treatment of B cell malignancies","authors":"Nafiseh Maghsoodi , Mohammadrasul Zareinejad , Ali Golestan , Elham Mahmoudi Maymand , Amin Ramezani","doi":"10.1016/j.cellimm.2023.104787","DOIUrl":"https://doi.org/10.1016/j.cellimm.2023.104787","url":null,"abstract":"<div><p>The administration of blinatumomab was accompanied by several adverse effects, including activation of regulatory <em>T</em>-cells and cytokine storm. The objective of this study was to produce and evaluate a novel αCD8/CD19 BiTE (αCD8/CD19) with the potency to directly target CD8<sup>+</sup> <em>T</em>-cells. In-silico studies were utilized for determining proper folding, receptor binding, and structural stability of αCD8/CD19 protein. Western blotting and indirect surface staining were used to evaluate the size accuracy and binding potency of the purified protein. Functionality was assessed for granzyme B production, cytotoxicity, and proliferation. The<!--> <!-->αCD8/CD19<!--> <!-->recombinant protein was produced in the CHO-K1 cell line with a final concentration of 1.94 mg/l. The αCD8/CD19 bound to CD8<sup>+</sup> <span>and CD19</span><sup>+</sup> <!-->cell lines and induced significant granzyme B production, cytotoxic activity and proliferation potential in the presence of IL-2 and tumor target cells. The maximum CD8<sup>+</sup> <em>T</em>-cell biological activity was observed on the 10th day with 10:1 effector-to-target ratio.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"393 ","pages":"Article 104787"},"PeriodicalIF":4.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134656940","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}
{"title":"Ro52/TRIM21 – From host defense to autoimmunity","authors":"Emilia Holwek , Aleksandra Opinc-Rosiak , Joanna Sarnik , Joanna Makowska","doi":"10.1016/j.cellimm.2023.104776","DOIUrl":"10.1016/j.cellimm.2023.104776","url":null,"abstract":"<div><p>Ro52 (TRIM21) belongs to the ubiquitin ligase family. This protein plays a crucial role in many immunological processes, including antibody-dependent intracellular neutralization, synergy with the complement system, antiviral response, death mediation, oxidative stress response, and protein ubiquitination. Abnormal expression of TRIM21 can break immunological tolerance and lead to the production of autoantibodies against TRIM21. Antibodies against TRIM21 are detected in various autoimmune diseases, including Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), or myositis. However, anti-TRIM21 presence is not limited to autoimmune connective tissue disorders. It was observed in patients with malignancies, various cancerous processes, infectious diseases, and idiopathic interstitial pneumonia. The occurrence of TRIM21 autoantibodies is also associated with clinical features, such as the prevalence of interstitial lung diseases and cardiac or haematological involvement in connective tissue disorders. The purpose of this review was to summarize current knowledge of the immunological functions of TRIM21 and analyze the clinical implications of anti-TRIM21 antibodies in the disease course.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"393 ","pages":"Article 104776"},"PeriodicalIF":4.3,"publicationDate":"2023-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49674773","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}
{"title":"Variability of vaccine responsiveness in early life","authors":"Michael E Pichichero","doi":"10.1016/j.cellimm.2023.104777","DOIUrl":"10.1016/j.cellimm.2023.104777","url":null,"abstract":"<div><p>Vaccinations in early life elicit variable antibody and cellular immune responses, sometimes leaving fully vaccinated children unprotected against life-threatening infectious diseases. Specific immune cell populations and immune networks may have a critical period of development and calibration in a window of opportunity occurring during the first 100 days of early life. Among the early life determinants of vaccine responses, this review will focus on modifiable factors involving development of the infant microbiota and metabolome: antibiotic exposure, breast versus formula feeding, and Caesarian section versus vaginal delivery of newborns. How microbiota may serve as natural adjuvants for vaccine responses and how microbiota-derived metabolites influence vaccine responses are also reviewed. Early life poor vaccine responsiveness can be linked to increased infection susceptibility because both phenotypes share similar immunity dysregulation profiles. An early life pre-vaccination endotype, when interventions have the highest potential for success, should be sought that predicts vaccine response trajectories.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"393 ","pages":"Article 104777"},"PeriodicalIF":4.3,"publicationDate":"2023-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49688902","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}
Yun Zhu Bai , Benjamin J. Kopecky , Kory J. Lavine , Daniel Kreisel
{"title":"Ferroptosis in the post-transplantation inflammatory response","authors":"Yun Zhu Bai , Benjamin J. Kopecky , Kory J. Lavine , Daniel Kreisel","doi":"10.1016/j.cellimm.2023.104774","DOIUrl":"10.1016/j.cellimm.2023.104774","url":null,"abstract":"<div><p>Transplantation is a life-saving therapy for patients with end-stage organ disease. Successful outcomes after transplantation require mitigation of the post-transplant inflammatory response, limiting alloreactivity, and prevention of organ rejection. Traditional immunosuppressive regimens aim to dampen the adaptive immune response; however, recent studies have shown the feasibility and efficacy of targeting the innate immune response. Necroinflammation initiated by donor organ cell death is implicated as a critical mediator of primary graft dysfunction, acute rejection, and chronic rejection. Ferroptosis is a form of regulated cell death that triggers post-transplantation inflammation and drives the activation of both innate and adaptive immune cells. There is a growing acceptance of the clinical relevance of ferroptosis to solid organ transplantation. Modulating ferroptosis may be a potentially promising strategy to reduce complications after organ transplantation.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"393 ","pages":"Article 104774"},"PeriodicalIF":4.3,"publicationDate":"2023-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41232644","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}
Xinyao Zhang , Haiqi Chen , Jiawen Han , Zongren Wang , Yu Guo , Zhongyang Zhou , Rong Luo , Meiqin Dai , Wei Ou , Lingwu Chen , Lan Shao
{"title":"ATM-AMPKα mediated LAG-3 expression suppresses T cell function in prostate cancer","authors":"Xinyao Zhang , Haiqi Chen , Jiawen Han , Zongren Wang , Yu Guo , Zhongyang Zhou , Rong Luo , Meiqin Dai , Wei Ou , Lingwu Chen , Lan Shao","doi":"10.1016/j.cellimm.2023.104773","DOIUrl":"10.1016/j.cellimm.2023.104773","url":null,"abstract":"<div><p>Immunotherapy for prostate cancer (PCa) faces serious challenges. Therefore, the co-inhibitory receptors that regulate T cell function of PCa must be elucidated. Here we identified that the inhibitory receptor LAG3 was significantly induced in T cells from PCa patients. Gene array analysis revealed that insufficient ataxia telangiectasia mutated (ATM) gene expression in PCa T cells was responsible for the elevated LAG3 expression. Mechanistically, insufficient ATM expression impaired its ability to activate AMPKα signaling and CD4<sup>+</sup> T cell functions, which further enhances the binding of the transcription factors XBP1 and EGR2 to <em>LAG3</em> promoter. Reconstitution of ATM and inhibition of XBP1 or EGR2 in PCa T cells suppressed LAG3 expression and restored the effector function of CD4<sup>+</sup> T cells from PCa. Our study revealed the mechanism of LAG3 upregulation in CD4<sup>+</sup> T lymphocytes of PCa patients and may provide insights for the development of immunotherapeutic strategies for PCa treatment.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"393 ","pages":"Article 104773"},"PeriodicalIF":4.3,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49674772","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}
Maria V. Medeleanu , Yu Chen Qian , Theo J. Moraes , Padmaja Subbarao
{"title":"Early-immune development in asthma: A review of the literature","authors":"Maria V. Medeleanu , Yu Chen Qian , Theo J. Moraes , Padmaja Subbarao","doi":"10.1016/j.cellimm.2023.104770","DOIUrl":"10.1016/j.cellimm.2023.104770","url":null,"abstract":"<div><p>This review presents a comprehensive examination of the various factors contributing to the immunopathogenesis of asthma from the prenatal to preschool period. We focus on the contributions of genetic and environmental components as well as the role of the nasal and gut microbiome on immune development. Predisposing genetic factors, including inherited genes associated with increased susceptibility to asthma, are discussed alongside environmental factors such as respiratory viruses and pollutant exposure, which can trigger or exacerbate asthma symptoms. Furthermore, the intricate interplay between the nasal and gut microbiome and the immune system is explored, emphasizing their influence on allergic immune development and response to environmental stimuli. This body of literature underscores the necessity of a comprehensive approach to comprehend and manage asthma, as it emphasizes the interactions of multiple factors in immune development and disease progression.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"393 ","pages":"Article 104770"},"PeriodicalIF":4.3,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41192827","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}