Yifan Zhou, Yusra B Medik, B. Patel, D. Zamler, Sijie Chen, T. Chapman, Sarah Schneider, Rachel L. Babcock, Taylor T. Chrisikos, Laura M. Kahn, Allison M. Dyevoich, E. Park, Alexandria P. Cogdill, Daniel H Johnson, Sarah B. Johnson, K. Wani, D. Ledesma, C. Hudgens, Jingjing Wang, M. A. W. Khan, Aron Y Joon, W. Peng, Haiyan S. Li, R. Arora, Ximing Tang, M. G. Raso, Xuegong Zhang, W. Foo, M. Tetzlaff, G. Diehl, K. Clise-Dwyer, Elizabeth M Whitley, M. Gubin, J. Allison, P. Hwu, N. Ajami, A. Diab, J. Wargo, S. Watowich
{"title":"Intestinal toxicity to CTLA-4 blockade driven by IL-6 and myeloid infiltration","authors":"Yifan Zhou, Yusra B Medik, B. Patel, D. Zamler, Sijie Chen, T. Chapman, Sarah Schneider, Rachel L. Babcock, Taylor T. Chrisikos, Laura M. Kahn, Allison M. Dyevoich, E. Park, Alexandria P. Cogdill, Daniel H Johnson, Sarah B. Johnson, K. Wani, D. Ledesma, C. Hudgens, Jingjing Wang, M. A. W. Khan, Aron Y Joon, W. Peng, Haiyan S. Li, R. Arora, Ximing Tang, M. G. Raso, Xuegong Zhang, W. Foo, M. Tetzlaff, G. Diehl, K. Clise-Dwyer, Elizabeth M Whitley, M. Gubin, J. Allison, P. Hwu, N. Ajami, A. Diab, J. Wargo, S. Watowich","doi":"10.1158/1538-7445.am2022-5545","DOIUrl":"https://doi.org/10.1158/1538-7445.am2022-5545","url":null,"abstract":"Zhou et al. establish murine models of anti-CTLA-4–mediated intestinal irAEs. These reveal common immune signatures and the importance of fecal microbiome dysbiosis as irAE-driving mechanisms, which enable preclinical therapeutic interventions. Key immune features are validated in a cohort of melanoma patients with ICB-associated intestinal irAEs.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":"106 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86249096","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}
Yang Zhang, Y. Ye, Xiaoqiang Tang, Hui Wang, Toshiko Tanaka, R. Tian, Xufei Yang, Lun Wang, Ying Xiao, Xiaomin Hu, Ye Jin, H. Pang, Tian Du, Honghong Liu, Lihong Sun, Shuo Xiao, R. Dong, L. Ferrucci, Z. Tian, Shuyang Zhang
{"title":"CCL17 acts as a novel therapeutic target in pathological cardiac hypertrophy and heart failure","authors":"Yang Zhang, Y. Ye, Xiaoqiang Tang, Hui Wang, Toshiko Tanaka, R. Tian, Xufei Yang, Lun Wang, Ying Xiao, Xiaomin Hu, Ye Jin, H. Pang, Tian Du, Honghong Liu, Lihong Sun, Shuo Xiao, R. Dong, L. Ferrucci, Z. Tian, Shuyang Zhang","doi":"10.1084/jem.20200418","DOIUrl":"https://doi.org/10.1084/jem.20200418","url":null,"abstract":"Zhang et al. identified chemokine CCL17 as a contributor to age-related heart failure in humans and mice via regulating plasticity and differentiation of T cells. Their findings suggested CCL17 as a novel therapeutic target in age-related heart failure.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83179540","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}
Yiliang Chen, Jue Zhang, Weiguo Cui, Roy L Silverstein
{"title":"CD36, a signaling receptor and fatty acid transporter that regulates immune cell metabolism and fate.","authors":"Yiliang Chen, Jue Zhang, Weiguo Cui, Roy L Silverstein","doi":"10.1084/jem.20211314","DOIUrl":"10.1084/jem.20211314","url":null,"abstract":"<p><p>CD36 is a type 2 cell surface scavenger receptor widely expressed in many immune and non-immune cells. It functions as both a signaling receptor responding to DAMPs and PAMPs, as well as a long chain free fatty acid transporter. Recent studies have indicated that CD36 can integrate cell signaling and metabolic pathways through its dual functions and thereby influence immune cell differentiation and activation, and ultimately help determine cell fate. Its expression along with its dual functions in both innate and adaptive immune cells contribute to pathogenesis of common diseases, including atherosclerosis and tumor progression, which makes CD36 and its downstream effectors potential therapeutic targets. This review comprehensively examines the dual functions of CD36 in a variety of immune cells, especially macrophages and T cells. We also briefly discuss CD36 function in non-immune cells, such as adipocytes and platelets, which impact the immune system via intercellular communication. Finally, outstanding questions in this field are provided for potential directions of future studies.</p>","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9022290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75170283","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}
M. Boieri, A. Malishkevich, R. Guennoun, E. Marchese, Sanne Kroon, Kathryn E Trerice, Mary E. Awad, Jong Ho Park, Sowmya Iyer, J. Kreuzer, W. Haas, M. Rivera, S. Demehri
{"title":"CD4+ T helper 2 cells suppress breast cancer by inducing terminal differentiation","authors":"M. Boieri, A. Malishkevich, R. Guennoun, E. Marchese, Sanne Kroon, Kathryn E Trerice, Mary E. Awad, Jong Ho Park, Sowmya Iyer, J. Kreuzer, W. Haas, M. Rivera, S. Demehri","doi":"10.1084/jem.20201963","DOIUrl":"https://doi.org/10.1084/jem.20201963","url":null,"abstract":"Boieri et al. demonstrate that CD4+ T helper cells directly block breast cancer development by forcing the cancer cells to terminally differentiate.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73481666","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}
{"title":"Dietary intervention preserves β cell function in mice through CTCF-mediated transcriptional reprogramming","authors":"Ruo-Ran Wang, Xinyuan Qiu, Ran Pan, Hongxing Fu, Ziyin Zhang, Qintao Wang, Haide Chen, Qing-Qian Wu, Xiaowen Pan, Yanping Zhou, Pengfei Shan, Shusen Wang, Guoji Guo, Min Zheng, Lingyun Zhu, Z. Meng","doi":"10.1084/jem.20211779","DOIUrl":"https://doi.org/10.1084/jem.20211779","url":null,"abstract":"Wang et al. systematically characterize the dynamic nature of β cell functional and transcriptomic adaptation along the progression of diet-induced obesity and T2D. They also identify CTCF as a key mediator of dietary intervention–induced preservation β cell function via transcriptional reprogramming.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":"52 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88977023","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}
Yuriko Otake-Kasamoto, H. Kayama, T. Kishikawa, S. Shinzaki, T. Tashiro, Takahiro Amano, M. Tani, T. Yoshihara, Bo Li, Haruka Tani, Li Liu, Akio Hayashi, D. Okuzaki, D. Motooka, S. Nakamura, Y. Okada, H. Iijima, K. Takeda, T. Takehara
{"title":"Lysophosphatidylserines derived from microbiota in Crohn’s disease elicit pathological Th1 response","authors":"Yuriko Otake-Kasamoto, H. Kayama, T. Kishikawa, S. Shinzaki, T. Tashiro, Takahiro Amano, M. Tani, T. Yoshihara, Bo Li, Haruka Tani, Li Liu, Akio Hayashi, D. Okuzaki, D. Motooka, S. Nakamura, Y. Okada, H. Iijima, K. Takeda, T. Takehara","doi":"10.1084/jem.20211291","DOIUrl":"https://doi.org/10.1084/jem.20211291","url":null,"abstract":"This study shows that Crohn’s disease–associated microbiota generate lysophosphatidylserines that promote Th1 responses by fueling glycolysis. Lysophosphatidylserine-induced aggravation of colitis is prevented by P2y10 deficiency in CD4+ T cells, demonstrating that dysbiotic microbiota-derived LysoPS exacerbates colitis by modulating Th1 cell metabolism.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73506710","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}
{"title":"Realigning the LIGHT signaling network to control dysregulated inflammation","authors":"C. Ware, M. Croft, G. Neil","doi":"10.1084/jem.20220236","DOIUrl":"https://doi.org/10.1084/jem.20220236","url":null,"abstract":"The cytokine LIGHT (TNFSF14) has emerged as an important modulator of innate and adaptive immune responses. Accumulating basic and clinical evidence points to the dysregulation of the LIGHT network as a disease-driving mechanism and supports the application of target-modifying therapeutics for disease intervention.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":"64 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89773041","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}
A. Onnis, Emanuele Andreano, Chiara Cassioli, Elisa Pantano, Valentina Abbiento, G. Marotta, R. Rappuoli, C. Baldari
{"title":"SARS-CoV-2 Spike protein suppresses CTL-mediated killing by inhibiting immune synapse assembly","authors":"A. Onnis, Emanuele Andreano, Chiara Cassioli, Elisa Pantano, Valentina Abbiento, G. Marotta, R. Rappuoli, C. Baldari","doi":"10.1101/2022.05.20.492764","DOIUrl":"https://doi.org/10.1101/2022.05.20.492764","url":null,"abstract":"CTL-mediated killing of virally infected or malignant cells is orchestrated at a specialized intercellular junction, the immune synapse (IS). We hypothesized that SARS-CoV-2 may target IS assembly in CTLs to escape killing. We show that primary human CD8+ T cells strongly upregulate the expression of ACE2, the Spike protein receptor, during differentiation to CTLs. CTL pre-incubation with the Wuhan or Omicron Spike variants inhibits IS assembly and function, as shown by defective synaptic accumulation of TCRs and tyrosine phosphoproteins as well as defective centrosome and lytic granule polarisation to the IS, resulting in impaired target cell killing. These defects were reversed by anti-Spike antibodies that interfere with ACE2 binding and were reproduced by ACE2 engagement with Angiotensin-II or an anti-ACE2 antibody, but not by the ACE2 product Ang (1-7). These results highlight a new strategy of immune evasion by SARS-CoV-2 based on the Spike-dependent, ACE2-mediated targeting of the lytic IS to prevent the elimination of infected cells. Summary statement We report a new mechanism of immune evasion by SARS-CoV-2 based on direct disabling CTLs to form immune synapses through Spike protein binding to ACE2. This mechanism could contribute to the failure of the immune system to control SARS-CoV-2 infection.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89612763","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}
Nicholas Hanuscheck, Carine Thalman, M. Domingues, Samantha Schmaul, M. Muthuraman, Florian Hetsch, Manuela Ecker, Heiko Endle, Mohammadsaleh Oshaghi, G. Martino, T. Kuhlmann, K. Bozek, Tim van Beers, S. Bittner, Jakob von Engelhardt, J. Vogt, C. Vogelaar, F. Zipp
{"title":"Interleukin-4 receptor signaling modulates neuronal network activity","authors":"Nicholas Hanuscheck, Carine Thalman, M. Domingues, Samantha Schmaul, M. Muthuraman, Florian Hetsch, Manuela Ecker, Heiko Endle, Mohammadsaleh Oshaghi, G. Martino, T. Kuhlmann, K. Bozek, Tim van Beers, S. Bittner, Jakob von Engelhardt, J. Vogt, C. Vogelaar, F. Zipp","doi":"10.1084/jem.20211887","DOIUrl":"https://doi.org/10.1084/jem.20211887","url":null,"abstract":"Neuroimmune interaction influences essential CNS processes. Hanuscheck et al. report on the expression of interleukin-4 receptor alpha at presynaptic terminals in mouse and the human brain. The modulation of neuronal IL-4R signaling alters the neuronal transcriptome, impacts synaptic transmission, and causes anxiety-related behavior.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73666337","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}
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