IL-17 promotes collagen deposition by cancer-associated fibroblasts and enhances immune exclusion of tumors.
IL-17促进癌症相关成纤维细胞的胶原沉积，增强肿瘤的免疫排斥。
{"title":"Matrix reboot: IL-17 signals CAFs to create a second tumor T cell checkpoint","authors":"M. McGeachy","doi":"10.1084/jem.20220444","DOIUrl":"https://doi.org/10.1084/jem.20220444","url":null,"abstract":"IL-17 promotes collagen deposition by cancer-associated fibroblasts and enhances immune exclusion of tumors.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73731252","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}
R. Hasebe, K. Murakami, Masaya Harada, N. Halaka, H. Nakagawa, F. Kawano, Y. Ohira, T. Kawamoto, F. Yull, T. Blackwell, J. Nio-Kobayashi, Toshihiko Iwanaga, Masahiko Watanabe, N. Watanabe, H. Hotta, T. Yamashita, D. Kamimura, Yuki Tanaka, M. Murakami
Local inflammation spreads to remote positions via sensory neuron–interneuron crosstalk using ATP. This neural pathway, or remote inflammation gateway reflex, may be a therapeutic target for inflammatory diseases with remote inflammation, such as rheumatoid arthritis.
{"title":"ATP spreads inflammation to other limbs through crosstalk between sensory neurons and interneurons","authors":"R. Hasebe, K. Murakami, Masaya Harada, N. Halaka, H. Nakagawa, F. Kawano, Y. Ohira, T. Kawamoto, F. Yull, T. Blackwell, J. Nio-Kobayashi, Toshihiko Iwanaga, Masahiko Watanabe, N. Watanabe, H. Hotta, T. Yamashita, D. Kamimura, Yuki Tanaka, M. Murakami","doi":"10.1084/jem.20212019","DOIUrl":"https://doi.org/10.1084/jem.20212019","url":null,"abstract":"Local inflammation spreads to remote positions via sensory neuron–interneuron crosstalk using ATP. This neural pathway, or remote inflammation gateway reflex, may be a therapeutic target for inflammatory diseases with remote inflammation, such as rheumatoid arthritis.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86780798","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}
Yikun Yao, Ping Du Jiang, B. Chao, D. Çağdaş, S. Kubo, Arasu Balasubramaniyam, Yu Zhang, B. Shadur, A. NaserEddin, L. Folio, Benjamin Schwarz, Eric Bohrnsen, Lixin Zheng, Matthew Lynberg, Simone Gottlieb, Michael A. Leney-Greene, Ann Y. Park, I. Tezcan, A. Akdoğan, R. Gocmen, S. Onder, A. Rosenberg, E. Soilleux, Errin Johnson, P. Jackson, J. Demeter, Samuel D. Chauvin, F. Paul, M. Selbach, H. Bulut, M. Clatworthy, Z. Tuong, Hanlin Zhang, B. Stewart, C. Bosio, P. Stepensky, S. Clare, S. Ganesan, J. Pascall, O. Daumke, G. Butcher, A. McMichael, A. Simon, M. Lenardo
Yao et al. describe GIMAP6 deficiency in humans and mice showing immune dysfunction and susceptibility to bacterial infections. They find impaired autophagy in GIMAP6-deficient immune cells and define a functional complex composed of GIMAP6, GIMAP7, and GABARAPL2.
{"title":"GIMAP6 regulates autophagy, immune competence, and inflammation in mice and humans","authors":"Yikun Yao, Ping Du Jiang, B. Chao, D. Çağdaş, S. Kubo, Arasu Balasubramaniyam, Yu Zhang, B. Shadur, A. NaserEddin, L. Folio, Benjamin Schwarz, Eric Bohrnsen, Lixin Zheng, Matthew Lynberg, Simone Gottlieb, Michael A. Leney-Greene, Ann Y. Park, I. Tezcan, A. Akdoğan, R. Gocmen, S. Onder, A. Rosenberg, E. Soilleux, Errin Johnson, P. Jackson, J. Demeter, Samuel D. Chauvin, F. Paul, M. Selbach, H. Bulut, M. Clatworthy, Z. Tuong, Hanlin Zhang, B. Stewart, C. Bosio, P. Stepensky, S. Clare, S. Ganesan, J. Pascall, O. Daumke, G. Butcher, A. McMichael, A. Simon, M. Lenardo","doi":"10.1084/jem.20201405","DOIUrl":"https://doi.org/10.1084/jem.20201405","url":null,"abstract":"Yao et al. describe GIMAP6 deficiency in humans and mice showing immune dysfunction and susceptibility to bacterial infections. They find impaired autophagy in GIMAP6-deficient immune cells and define a functional complex composed of GIMAP6, GIMAP7, and GABARAPL2.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89330039","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}
As the first immune cells to colonize tissues and long-lived resident cells, macrophages play important roles in tissue functions during early development, homeostasis, and disease. Here, Chakarov et al. discuss macrophage origin and functions in adipose tissue and how these features are modulated in obesity.
{"title":"Role of adipose tissue macrophages in obesity-related disorders","authors":"S. Chakarov, Camille Blériot, F. Ginhoux","doi":"10.1084/jem.20211948","DOIUrl":"https://doi.org/10.1084/jem.20211948","url":null,"abstract":"As the first immune cells to colonize tissues and long-lived resident cells, macrophages play important roles in tissue functions during early development, homeostasis, and disease. Here, Chakarov et al. discuss macrophage origin and functions in adipose tissue and how these features are modulated in obesity.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76313113","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}
Reporting the distribution and inclusion of both males and females in immunology and infectious diseases research is improving, but rigorous analyses of differential outcomes between males and females, including mechanistic inquiries into the causes of sex differences, still lags behind.
{"title":"Sex biases in infectious diseases research","authors":"S. Dhakal, Sabal Chaulagain, S. Klein","doi":"10.1084/jem.20211486","DOIUrl":"https://doi.org/10.1084/jem.20211486","url":null,"abstract":"Reporting the distribution and inclusion of both males and females in immunology and infectious diseases research is improving, but rigorous analyses of differential outcomes between males and females, including mechanistic inquiries into the causes of sex differences, still lags behind.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84309407","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}
Pub Date : 2022-05-02Epub Date: 2022-04-13DOI: 10.1084/jem.20211515
Gabrielle Rizzuto, Adrian Erlebacher
The paradox of fetomaternal tolerance has puzzled immunologists and reproductive biologists alike for almost 70 yr. Even the idea that the conceptus evokes a uniformly tolerogenic immune response in the mother is contradicted by the long-appreciated ability of pregnant women to mount robust antibody responses to paternal HLA molecules and RBC alloantigens such as Rh(D). Synthesizing these older observations with more recent work in mice, we discuss how the decision between tolerance or immunity to a given fetoplacental antigen appears to be a function of whether the antigen is trophoblast derived-and thus decorated with immunosuppressive glycans-or fetal blood cell derived.
{"title":"Trophoblast antigens, fetal blood cell antigens, and the paradox of fetomaternal tolerance.","authors":"Gabrielle Rizzuto, Adrian Erlebacher","doi":"10.1084/jem.20211515","DOIUrl":"10.1084/jem.20211515","url":null,"abstract":"<p><p>The paradox of fetomaternal tolerance has puzzled immunologists and reproductive biologists alike for almost 70 yr. Even the idea that the conceptus evokes a uniformly tolerogenic immune response in the mother is contradicted by the long-appreciated ability of pregnant women to mount robust antibody responses to paternal HLA molecules and RBC alloantigens such as Rh(D). Synthesizing these older observations with more recent work in mice, we discuss how the decision between tolerance or immunity to a given fetoplacental antigen appears to be a function of whether the antigen is trophoblast derived-and thus decorated with immunosuppressive glycans-or fetal blood cell derived.</p>","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9011327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75536869","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}
Pub Date : 2022-05-02Epub Date: 2022-04-14DOI: 10.1084/jem.20211681
Joseph Kelich, Tomas Aramburu, Joanne J van der Vis, Louise Showe, Andrew Kossenkov, Jasper van der Smagt, Maarten Massink, Angela Schoemaker, Eric Hennekam, Marcel Veltkamp, Coline H M van Moorsel, Emmanuel Skordalakes
Exonic sequencing identified a family with idiopathic pulmonary fibrosis (IPF) containing a previously unreported heterozygous mutation in POT1 p.(L259S). The family displays short telomeres and genetic anticipation. We found that POT1(L259S) is defective in binding the telomeric overhang, nuclear accumulation, negative regulation of telomerase, and lagging strand maintenance. Patient cells containing the mutation display telomere loss, lagging strand defects, telomere-induced DNA damage, and premature senescence with G1 arrest. Our data suggest POT1(L259S) is a pathogenic driver of IPF and provide insights into gene therapy options.
{"title":"Telomere dysfunction implicates POT1 in patients with idiopathic pulmonary fibrosis.","authors":"Joseph Kelich, Tomas Aramburu, Joanne J van der Vis, Louise Showe, Andrew Kossenkov, Jasper van der Smagt, Maarten Massink, Angela Schoemaker, Eric Hennekam, Marcel Veltkamp, Coline H M van Moorsel, Emmanuel Skordalakes","doi":"10.1084/jem.20211681","DOIUrl":"10.1084/jem.20211681","url":null,"abstract":"<p><p>Exonic sequencing identified a family with idiopathic pulmonary fibrosis (IPF) containing a previously unreported heterozygous mutation in POT1 p.(L259S). The family displays short telomeres and genetic anticipation. We found that POT1(L259S) is defective in binding the telomeric overhang, nuclear accumulation, negative regulation of telomerase, and lagging strand maintenance. Patient cells containing the mutation display telomere loss, lagging strand defects, telomere-induced DNA damage, and premature senescence with G1 arrest. Our data suggest POT1(L259S) is a pathogenic driver of IPF and provide insights into gene therapy options.</p>","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9014792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75423007","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}
Pub Date : 2022-05-02Epub Date: 2022-03-30DOI: 10.1084/jem.20211830
Madeline J Churchill, Haley du Bois, Taylor A Heim, Tenny Mudianto, Maria M Steele, Jeffrey C Nolz, Amanda W Lund
Lymphatic vessels are often considered passive conduits that flush antigenic material, pathogens, and cells to draining lymph nodes. Recent evidence, however, suggests that lymphatic vessels actively regulate diverse processes from antigen transport to leukocyte trafficking and dietary lipid absorption. Here we tested the hypothesis that infection-induced changes in lymphatic transport actively contribute to innate host defense. We demonstrate that cutaneous vaccinia virus infection by scarification activates dermal lymphatic capillary junction tightening (zippering) and lymph node lymphangiogenesis, which are associated with reduced fluid transport and cutaneous viral sequestration. Lymphatic-specific deletion of VEGFR2 prevented infection-induced lymphatic capillary zippering, increased fluid flux out of tissue, and allowed lymphatic dissemination of virus. Further, a reduction in dendritic cell migration to lymph nodes in the absence of lymphatic VEGFR2 associated with reduced antiviral CD8+ T cell expansion. These data indicate that VEGFR2-driven lymphatic remodeling is a context-dependent, active mechanism of innate host defense that limits viral dissemination and facilitates protective, antiviral CD8+ T cell responses.
淋巴管通常被认为是将抗原物质、病原体和细胞冲向引流淋巴结的被动通道。然而，最近的证据表明，淋巴管能主动调节从抗原转运到白细胞贩运和食物脂质吸收等各种过程。在这里，我们测试了感染诱导的淋巴运输变化积极促进先天宿主防御的假设。我们证明，通过瘢痕感染皮肤疫苗病毒会激活真皮淋巴毛细血管交界处收紧（拉链）和淋巴结淋巴管生成，这与体液运输减少和皮肤病毒螯合有关。淋巴特异性删除 VEGFR2 可阻止感染诱导的淋巴毛细血管拉链，增加组织液流出，并允许病毒通过淋巴传播。此外，在缺乏淋巴 VEGFR2 的情况下，树突状细胞向淋巴结迁移的减少与抗病毒 CD8+ T 细胞扩增的减少有关。这些数据表明，VEGFR2 驱动的淋巴重塑是先天宿主防御的一种环境依赖性主动机制，它能限制病毒传播并促进保护性的抗病毒 CD8+ T 细胞反应。
{"title":"Infection-induced lymphatic zippering restricts fluid transport and viral dissemination from skin.","authors":"Madeline J Churchill, Haley du Bois, Taylor A Heim, Tenny Mudianto, Maria M Steele, Jeffrey C Nolz, Amanda W Lund","doi":"10.1084/jem.20211830","DOIUrl":"10.1084/jem.20211830","url":null,"abstract":"<p><p>Lymphatic vessels are often considered passive conduits that flush antigenic material, pathogens, and cells to draining lymph nodes. Recent evidence, however, suggests that lymphatic vessels actively regulate diverse processes from antigen transport to leukocyte trafficking and dietary lipid absorption. Here we tested the hypothesis that infection-induced changes in lymphatic transport actively contribute to innate host defense. We demonstrate that cutaneous vaccinia virus infection by scarification activates dermal lymphatic capillary junction tightening (zippering) and lymph node lymphangiogenesis, which are associated with reduced fluid transport and cutaneous viral sequestration. Lymphatic-specific deletion of VEGFR2 prevented infection-induced lymphatic capillary zippering, increased fluid flux out of tissue, and allowed lymphatic dissemination of virus. Further, a reduction in dendritic cell migration to lymph nodes in the absence of lymphatic VEGFR2 associated with reduced antiviral CD8+ T cell expansion. These data indicate that VEGFR2-driven lymphatic remodeling is a context-dependent, active mechanism of innate host defense that limits viral dissemination and facilitates protective, antiviral CD8+ T cell responses.</p>","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8972184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78855850","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}
Masahiko Nishitani-Isa, Kojiro Mukai, Y. Honda, H. Nihira, Takayuki Tanaka, H. Shibata, K. Kodama, E. Hiejima, K. Izawa, Yuri Kawasaki, M. Osawa, Yu Katata, Sachiko Onodera, Tatsuya Watanabe, T. Uchida, S. Kure, J. Takita, O. Ohara, M. Saito, R. Nishikomori, T. Taguchi, Y. Sasahara, T. Yasumi
Using induced pluripotent stem cells carrying CDC42R186C, trapping of CDC42 C-terminal variants within the Golgi apparatus is shown to trigger autoinflammation by promoting pyrin inflammasome assembly through a mechanism independent of their GTPase activity.
{"title":"Trapping of CDC42 C-terminal variants in the Golgi drives pyrin inflammasome hyperactivation","authors":"Masahiko Nishitani-Isa, Kojiro Mukai, Y. Honda, H. Nihira, Takayuki Tanaka, H. Shibata, K. Kodama, E. Hiejima, K. Izawa, Yuri Kawasaki, M. Osawa, Yu Katata, Sachiko Onodera, Tatsuya Watanabe, T. Uchida, S. Kure, J. Takita, O. Ohara, M. Saito, R. Nishikomori, T. Taguchi, Y. Sasahara, T. Yasumi","doi":"10.1084/jem.20211889","DOIUrl":"https://doi.org/10.1084/jem.20211889","url":null,"abstract":"Using induced pluripotent stem cells carrying CDC42R186C, trapping of CDC42 C-terminal variants within the Golgi apparatus is shown to trigger autoinflammation by promoting pyrin inflammasome assembly through a mechanism independent of their GTPase activity.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73056184","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}
CD36 functions as both a signaling receptor and fatty acid transporter in various immune and non-immune cells. This review summarizes how its dual functions determine immune cell functions and fates, which contribute to common diseases including atherosclerosis and tumor progression.
{"title":"CD36, a signaling receptor and fatty acid transporter that regulates immune cell metabolism and fate","authors":"Yiliang Chen, Jue Zhang, W. Cui, R. Silverstein","doi":"10.1084/jem.20211314","DOIUrl":"https://doi.org/10.1084/jem.20211314","url":null,"abstract":"CD36 functions as both a signaling receptor and fatty acid transporter in various immune and non-immune cells. This review summarizes how its dual functions determine immune cell functions and fates, which contribute to common diseases including atherosclerosis and tumor progression.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75170283","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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