Discovery immunology最新文献

Granulomatous inflammatory responses are elicited in the liver of PD-1 knockout mice by de novo genome mutagenesis. PD-1基因敲除小鼠肝脏中的肉芽肿炎症反应是通过从头基因组突变引起的。

Discovery immunology Pub Date : 2024-12-25 eCollection Date: 2025-01-01 DOI: 10.1093/discim/kyae018

Ilamangai Nagaretnam, Yoshiya Kakimoto, Azusa Yoneshige, Fuka Takeuchi, Takayuki Sakimura, Kanato Sato, Yoshiro Osaki, Yuta Ishii, Ai Ozaki, Masaru Tamura, Michito Hamada, Toshiaki Shigeoka, Akihiko Ito, Yasumasa Ishida

{"title":"Granulomatous inflammatory responses are elicited in the liver of PD-1 knockout mice by de novo genome mutagenesis.","authors":"Ilamangai Nagaretnam, Yoshiya Kakimoto, Azusa Yoneshige, Fuka Takeuchi, Takayuki Sakimura, Kanato Sato, Yoshiro Osaki, Yuta Ishii, Ai Ozaki, Masaru Tamura, Michito Hamada, Toshiaki Shigeoka, Akihiko Ito, Yasumasa Ishida","doi":"10.1093/discim/kyae018","DOIUrl":"10.1093/discim/kyae018","url":null,"abstract":"Introduction: Programmed death-1 (PD-1) is a negative regulator of immune responses. Upon deletion of PD-1 in mice, symptoms of autoimmunity developed only after they got old. In a model experiment in cancer immunotherapy, PD-1 was shown to prevent cytotoxic T lymphocytes from attacking cancer cells that expressed neoantigens derived from genome mutations. Furthermore, the larger number of genome mutations in cancer cells led to more robust anti-tumor immune responses after the PD-1 blockade. To understand the common molecular mechanisms underlying these findings, we hypothesize that we might have acquired PD-1 during evolution to avoid/suppress autoimmune reactions against neoantigens derived from mutations in the genome of aged individuals.Methods: To test the hypothesis, we introduced random mutations into the genome of young PD-1-/- and PD-1+/+ mice. We employed two different procedures of random mutagenesis: administration of a potent chemical mutagen N-ethyl-N-nitrosourea (ENU) into the peritoneal cavity of mice and deletion of MSH2, which is essential for the mismatch-repair activity in the nucleus and therefore for the suppression of accumulation of random mutations in the genome.Results: We observed granulomatous inflammatory changes in the liver of the ENU-treated PD-1 knockout (KO) mice but not in the wild-type (WT) counterparts. Such lesions also developed in the PD-1/MSH2 double KO mice but not in the MSH2 single KO mice.Conclusion: These results support our hypothesis about the physiological function of PD-1 and address the mechanistic reasons for immune-related adverse events observed in cancer patients having PD-1-blockade immunotherapies.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"4 1","pages":"kyae018"},"PeriodicalIF":0.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The sedoheptulose kinase CARKL controls T-cell cytokine outputs and migration by promoting metabolic reprogramming. sedoheptulose kinase CARKL通过促进代谢重编程来控制t细胞细胞因子的输出和迁移。

Discovery immunology Pub Date : 2024-11-19 eCollection Date: 2024-01-01 DOI: 10.1093/discim/kyae016

Michelangelo Certo, Jennifer Niven, Robert Haas, Paula Rudzinska, Joanne Smith, Danilo Cucchi, Jose R Hombrebueno, Claudio Mauro

{"title":"The sedoheptulose kinase CARKL controls T-cell cytokine outputs and migration by promoting metabolic reprogramming.","authors":"Michelangelo Certo, Jennifer Niven, Robert Haas, Paula Rudzinska, Joanne Smith, Danilo Cucchi, Jose R Hombrebueno, Claudio Mauro","doi":"10.1093/discim/kyae016","DOIUrl":"10.1093/discim/kyae016","url":null,"abstract":"Background: Immunometabolism is a crucial determinant of immune cell function, influencing cellular activation and differentiation through metabolic pathways. The intricate interplay between metabolism and immune responses is highlighted by the distinct metabolic programs utilized by immune cells to support their functions. Of particular interest is the pentose phosphate pathway (PPP), a key metabolic pathway branching out of glycolysis that plays a pivotal role in generating NADPH and pentose sugars crucial for antioxidant defense and biosynthesis. The sedoheptulose kinase Carbohydrate Kinase-like protein (CARKL), an enzyme involved in the PPP, emerges as a critical regulator of cell metabolism and was previously shown to play a role in macrophage function.Methods: This study delves into the impact of CARKL expression on T-cell functionality, revealing dynamic alterations in response to cellular activation. Notably, CARKL overexpression leads to significant metabolic shifts in T cells, affecting mitochondrial respiration, ATP production, and inflammatory cytokine profiles. Furthermore, CARKL modulation influences T-cell motility by regulating chemokine receptor expression, particularly compromising CXCR3 expression and impairing T-cell migration in response to specific chemokine signals.Conclusions: These findings underscore the multifaceted role of CARKL as a metabolic regulator shaping T-cell responses. Overall, our data reveal the complex regulatory mechanisms orchestrated by CARKL in T-cell function, with implications for immune regulation. Further exploration of the molecular interactions between CARKL and metabolic reprogramming in T cells could provide valuable insights into immune regulation and potential therapeutic strategies.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"3 1","pages":"kyae016"},"PeriodicalIF":0.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11635167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

How (Eco)immunology can augment global EcoHealth programmes: opportunities, needs, and challenges. 生态）免疫学如何增强全球生态健康计划：机遇、需求和挑战。

Discovery immunology Pub Date : 2024-10-15 eCollection Date: 2024-01-01 DOI: 10.1093/discim/kyae015

Sheena M Cruickshank, Kathryn J Else, Iris Mair, Holly Shiels, Susanne Shultz

引用次数: 0

Unravelling monocyte functions: from the guardians of health to the regulators of disease. 揭示单核细胞的功能：从健康的守护者到疾病的调节者。

Discovery immunology Pub Date : 2024-08-30 eCollection Date: 2024-01-01 DOI: 10.1093/discim/kyae014

Alexander Mildner, Ki-Wook Kim, Simon Yona

引用次数: 0

Identification of a transcription factor network regulating anti-TNF mediated IL10 expression in human CD4+ T cells 识别调控人类 CD4+ T 细胞中由抗肿瘤坏死因子介导的 IL10 表达的转录因子网络

Discovery immunology Pub Date : 2024-07-27 DOI: 10.1093/discim/kyae013

G. A. Povoleri, M. Ridley, Rebecca J Marrow, Sylvine Lalnunhlimi, Sarah E. Ryan, Audrey Kelly, Paul Lavender, L. Taams

{"title":"Identification of a transcription factor network regulating anti-TNF mediated IL10 expression in human CD4+ T cells","authors":"G. A. Povoleri, M. Ridley, Rebecca J Marrow, Sylvine Lalnunhlimi, Sarah E. Ryan, Audrey Kelly, Paul Lavender, L. Taams","doi":"10.1093/discim/kyae013","DOIUrl":"https://doi.org/10.1093/discim/kyae013","url":null,"abstract":"\u0000 CD4+ T cells are key players in immune-mediated inflammatory diseases (IMIDs) through production of inflammatory mediators including TNF. Anti-TNF therapy has revolutionised the treatment of several IMIDs and we previously demonstrated that in vitro treatment of human CD4+ T cells with anti-TNF promotes anti-inflammatory IL-10 expression in multiple subpopulations of CD4+ T cells. Here we investigated the transcriptional mechanisms underlying the IL-10 induction by TNF-blockade in CD4+ T cells, isolated from PBMCs of healthy volunteers, stimulated in vitro for 3 days with anti-CD3/CD28 mAb in the absence or presence of anti-TNF. After culture, CD45RA+ cells were depleted before performing gene expression profiling and chromatin accessibility analysis. Gene expression analysis of CD45RA-CD4+ T cells showed a distinct anti-TNF specific gene signature of 183 genes (q-value <0.05). Pathway enrichment analysis of differentially expressed genes revealed multiple pathways related to cytokine signalling and regulation of cytokine production; in particular, IL10 was the most upregulated gene by anti-TNF, while the proinflammatory cytokines and chemokines IFNG, IL9, IL22 and CXCL10 were significantly downregulated (q-value <0.05). Transcription factor motif analysis at the differentially open chromatin regions, after anti-TNF treatment, revealed 58 transcription factor motifs enriched at the IL10 locus. We identified seven transcription factor candidates for the anti-TNF mediated regulation of IL-10, which were either differentially expressed or whose locus was differentially accessible upon anti-TNF treatment. Correlation analysis between the expression of these transcription factors and IL10 suggests a role for MAF, PRDM1 and/or EOMES in regulating IL10 expression in CD4+ T cells upon anti-TNF treatment.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"78 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141798170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to: Lunar-linked biological rhythms in the immune system of freshwater three-spined stickleback. 更正：淡水三刺鱼免疫系统的月相生物节律

Discovery immunology Pub Date : 2024-07-15 eCollection Date: 2024-01-01 DOI: 10.1093/discim/kyae012

引用次数: 0

Assessing immune phenotypes using simple proxy measures: promise and limitations. 使用简单的替代措施评估免疫表型：前景与局限。

Discovery immunology Pub Date : 2024-06-28 eCollection Date: 2024-01-01 DOI: 10.1093/discim/kyae010

Alexander E Downie, Ramya S Barre, Annie Robinson, Jennie Yang, Ying-Han Chen, Jian-Da Lin, Oyebola Oyesola, Frank Yeung, Ken Cadwell, P'ng Loke, Andrea L Graham

{"title":"Assessing immune phenotypes using simple proxy measures: promise and limitations.","authors":"Alexander E Downie, Ramya S Barre, Annie Robinson, Jennie Yang, Ying-Han Chen, Jian-Da Lin, Oyebola Oyesola, Frank Yeung, Ken Cadwell, P'ng Loke, Andrea L Graham","doi":"10.1093/discim/kyae010","DOIUrl":"10.1093/discim/kyae010","url":null,"abstract":"The study of immune phenotypes in wild animals is beset by numerous methodological challenges, with assessment of detailed aspects of phenotype difficult to impossible. This constrains the ability of disease ecologists and ecoimmunologists to describe immune variation and evaluate hypotheses explaining said variation. The development of simple approaches that allow characterization of immune variation across many populations and species would be a significant advance. Here we explore whether serum protein concentrations and coarse-grained white blood cell profiles, immune quantities that can easily be assayed in many species, can predict, and therefore serve as proxies for, lymphocyte composition properties. We do this in rewilded laboratory mice, which combine the benefits of immune phenotyping of lab mice with the natural context and immune variation found in the wild. We find that easily assayed immune quantities are largely ineffective as predictors of lymphocyte composition, either on their own or with other covariates. Immunoglobulin G (IgG) concentration and neutrophil-lymphocyte ratio show the most promise as indicators of other immune traits, but their explanatory power is limited. Our results prescribe caution in inferring immune phenotypes beyond what is directly measured, but they do also highlight some potential paths forward for the development of proxy measures employable by ecoimmunologists.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"3 1","pages":"kyae010"},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11264049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141753524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Extracellular vesicles: an emerging tool for wild immunology. 细胞外囊泡：野生免疫学的新兴工具。

Discovery immunology Pub Date : 2024-06-24 eCollection Date: 2024-01-01 DOI: 10.1093/discim/kyae011

Camila Espejo, Vanessa O Ezenwa

{"title":"Extracellular vesicles: an emerging tool for wild immunology.","authors":"Camila Espejo, Vanessa O Ezenwa","doi":"10.1093/discim/kyae011","DOIUrl":"10.1093/discim/kyae011","url":null,"abstract":"The immune system is crucial for defending organisms against pathogens and maintaining health. Traditionally, research in immunology has relied on laboratory animals to understand how the immune system works. However, there is increasing recognition that wild animals, due to their greater genetic diversity, lifespan, and environmental exposures, have much to contribute to basic and translational immunology. Unfortunately, logistical challenges associated with collecting and storing samples from wildlife, and the lack of commercially available species-specific reagents have hindered the advancement of immunological research on wild species. Extracellular vesicles (EVs) are cell-derived nanoparticles present in all body fluids and tissues of organisms spanning from bacteria to mammals. Human and lab animal studies indicate that EVs are involved in a range of immunological processes, and recent work shows that EVs may play similar roles in diverse wildlife species. Thus, EVs can expand the toolbox available for wild immunology research, helping to overcome some of the challenges associated with this work. In this paper, we explore the potential application of EVs to wild immunology. First, we review current understanding of EV biology across diverse organisms. Next, we discuss key insights into the immune system gained from research on EVs in human and laboratory animal models and highlight emerging evidence from wild species. Finally, we identify research themes in wild immunology that can immediately benefit from the study of EVs and describe practical considerations for using EVs in wildlife research.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"3 1","pages":"kyae011"},"PeriodicalIF":0.0,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11244269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lunar-linked biological rhythms in the immune system of freshwater three-spined stickleback. 淡水三刺鱼免疫系统的月相生物节律

Discovery immunology Pub Date : 2024-05-25 eCollection Date: 2024-01-01 DOI: 10.1093/discim/kyae007

Joseph A Jackson, Alexander Stewart, Joanne Cable

{"title":"Lunar-linked biological rhythms in the immune system of freshwater three-spined stickleback.","authors":"Joseph A Jackson, Alexander Stewart, Joanne Cable","doi":"10.1093/discim/kyae007","DOIUrl":"10.1093/discim/kyae007","url":null,"abstract":"Immune responses are widely accepted to be under circadian regulation via a molecular clock, with many practical consequences, but much less is known of how other biological rhythms could affect the immune system. In this study, we search for lunar rhythms (circalunar, circasemilunar, and circatidal cycles) in the immune expression of the recently marine-derived freshwater fish, the low-plate morph of the three-spined stickleback. We employed time series of immune expression (mRNA) measurements for 14 immune-associated genes, representing a variety of immunological pathways. Times series measurements were taken on fish populations in the wild, in seminatural outdoor mesocosms, and in the laboratory, according to sampling regimens originally designed to study circannual variation but with the additional potential to provide information about lunar variation. Our evidence best supported the existence of a very small endogenous tidal rhythm. This is consistent with previous suggestions of the existence of a primordial tidal endogenous clock, some elements of which may be conserved in animals evolving outside the marine environment.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"3 1","pages":"kyae007"},"PeriodicalIF":0.0,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11165434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141307554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adapting for success: T cell features at tissue sites 适应成功：组织部位的 T 细胞特征

Discovery immunology Pub Date : 2024-05-18 DOI: 10.1093/discim/kyae009

Philip P Ahern, Emily Gwyer Findlay

引用次数: 0