Article
Biochemistry & Molecular Biology
Jixiu Wang, Qianhui Sun, Jian Zhang, Huanling Wang, Hong Liu
Summary: This study explored the biological activity of recombinant interleukin-6 (rmaIL-6) and soluble interleukin-6 receptor (rmasIL-6R) in grass carp cells and investigated their regulation of signaling pathways. The results showed that rmaIL-6 mainly activates the JAK/STAT3 pathway and not the MEK/ERK pathway. Additionally, the activation of the JAK2/STAT3 pathway was found to be essential for the generation of socs3a and socs3b induced by IL-6 trans-signaling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Yang Mei, Kehan Ren, Yijie Liu, Annabel Ma, Zongjun Xia, Xu Han, Ermin Li, Hamza Tariq, Haiyan Bao, Xinshu Xie, Cheng Zou, Dingxiao Zhang, Zhaofeng Li, Lili Dong, Amit Verma, Xinyan Lu, Yasmin Abaza, Jessica K. Altman, Madina Sukhanova, Jing Yang, Peng Ji
Summary: This study reveals that age-related MDS can transform into AML, and the cytokine IL-6 plays a significant role in this transformation. By studying a double knockout mouse model and high-risk MDS patients, blocking IL-6 signaling was found to significantly ameliorate AML progression, indicating the clinical significance of targeting IL-6 signaling in treating high-risk MDS.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Infectious Diseases
Hongli Zhou, Yuting Lu, Hang Wei, Yixin Chen, Yanin Limpanon, Paron Dekumyoy, Ping Huang, Peiyao Shi, Zhiyue Lv
Summary: This study explores the migration route and tissue damage caused by Angiostrongylus cantonensis (AC) in both permissive and nonpermissive hosts using various technologies. The findings show that in nonpermissive host mice, AC larvae migrate from the intestinal wall to the liver, then to the lungs, and finally to the brain. The migration process of the larvae causes acute and fatal pneumonia in the lungs, accompanied by activation of the Stat3/IL-6 signaling pathway. Additionally, sustained interstitial pneumonia and pulmonary fibrosis are observed in late-stage infection. Inhibition of Stat3/IL-6 signaling can attenuate AC-induced pneumonia in nonpermissive hosts. These findings provide important insights into the pathogenesis of AC infection and indicate potential strategies for intervention.
PLOS NEGLECTED TROPICAL DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Yang Zheng, Yunqi Li, Xianwen Ran, Di Wang, Xianghui Zheng, Maomao Zhang, Bo Yu, Yong Sun, Jian Wu
Summary: The study reveals that the m(6)A modification writer Mettl14 plays a critical role in macrophage inflammation in atherosclerosis through the NF-kappa B/IL-6 signaling pathway. Mettl14 regulates the stability of Myd88 mRNA and affects the distribution of p65 in nuclei, which in turn influences the expression of IL-6. Moreover, Mettl14 gene knockout reduces the inflammatory response of macrophages and the development of atherosclerotic plaques.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Endocrinology & Metabolism
Danny Luan, Benyamin Dadpey, Jessica Zaid, Pania E. Bridge-Comer, Julia H. DeLuca, Wenmin Xia, Joshua Castle, Shannon M. Reilly
Summary: The bidirectional interaction between adipocytes and adipose tissue immune cells is crucial for regulating adipose function, inflammation, and insulin responsiveness. Obesity reduces cAMP-driven IL-6 secretion from adipocytes, but restoring their catecholamine sensitivity can stimulate IL-6 secretion and activate macrophages to promote an anti-inflammatory gene expression pattern.
Article
Medicine, Research & Experimental
Olga A. Mareninova, Eszter T. Vegh, Natalia Shalbueva, Carli J. M. Wightman, Dustin L. Dillon, Sudarshan Malla, Yan Xie, Toshimasa Takahashi, Zoltan Rakonczay, Samuel W. French, Herbert Y. Gaisano, Fred S. Gorelick, Stephen J. Pandol, Steven J. Bensinger, Nicholas O. Davidson, David W. Dawson, Ilya Gukovsky, Anna S. Gukovskaya
Summary: The study reveals the essential role of the M6P pathway in maintaining exocrine pancreas homeostasis and function, with Gnptab(-/-) mice developing spontaneous pancreatitis. Normalization of cholesterol metabolism by pharmacologic means alleviated responses of experimental pancreatitis.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Medicine, Research & Experimental
Yu Hirata, Kazuhiro Nomura, Daisuke Kato, Hiroaki Wake, Wataru Ogawa, Yu Hirata, Yoshihisa Tachibana, Takahiro Niikura, Kana Uchiyama, Tetsuya Hosooka, Tomoaki Fukui, Keisuke Oe, Ryosuke Kuroda, Yuji Hara, Takahiro Adachi, Koji Shibasaki
Summary: This study reveals that the upregulation of KLF15 and IL-6, as well as the decrease in intracellular Ca2+ concentration, are involved in muscle atrophy induced by immobility. This finding has been validated in both mouse models and human samples.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Immunology
Wen-Wu Li, Yang Yang, Tian-Zhi Guo, Peyman Sahbaie, Xiao-you Shi, Qin Guang, Wade S. Kingery, Leonore A. Herzenberg, J. David Clark
Summary: In a murine tibia fracture model of complex regional pain syndrome (CRPS), up-regulated IL-6 signaling was found to be crucial for the development of nociceptive sensitization, vascular changes, and IgM immune complex deposition in the injured limbs. These findings suggest that anti-IL-6 therapies may be effective in reducing pain in the context of limb fracture or CRPS.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Article
Immunology
Hideaki Miyachi, Seiichiro Wakabayashi, Takashi Sugihira, Reika Aoyama, Shinobu Saijo, Hanako Koguchi-Yoshioka, Manabu Fujimoto, Gabriel Nunez, Hiroyuki Matsue, Yuumi Nakamura
Summary: The research demonstrated that Malassezia-induced IL-17-dependent skin inflammation and control of fungal infection are mediated via keratinocyte IL-36 receptor/MyD88 signaling using a new skin infection model.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Immunology
John G. Noel, Seth W. Ramser, Lori Pitstick, Holly S. Goetzman, Elizabeth L. Dale, Andrew Potter, Mike Adam, S. Steven Potter, Jason C. Gardner
Summary: This study demonstrates that the burn wound is the primary source of G-CSF and IL-6 secretion, and their secretion is independent through an IL-1/MyD88-dependent mechanism. IL-1/MyD88 signaling mediates postburn anemia by inducing G-CSF and IL-6 secretion, leading to impaired medullary erythropoiesis and limiting the access of erythroid cells to iron. Neutralizing IL-1a/b antibodies attenuate features of postburn anemia and restore deficits caused by burn injury.
JOURNAL OF IMMUNOLOGY
(2023)
Article
Cell Biology
Han-zhou Qi, Yi-ling Ye, Yuan Suo, Hong Qu, Hai-yan Zhang, Kai-bo Yang, Zhi-ping Fan, Fen Huang, Li Xuan, Yan-qiu Chen, Hua Jin, Qi-fa Liu
Summary: In active chronic graft-versus-host disease (cGVHD) patients, bone marrow-derived mesenchymal stem cells (BM-MSCs) exhibited abnormal differentiation characterized by increased osteogenic capacity and decreased adipogenic capacity. The upregulation of Wnt3a through the Wnt/beta-catenin signaling pathway in MSCs was identified as a potential underlying mechanism for this phenomenon.
CELL DEATH & DISEASE
(2021)
Article
Neurosciences
Jun Ma, Kai Li, Xue Sun, Jia-Nan Liang, Xian-Quan An, Meng Tian, Jing Li, Fang Yan, Yue Yin, Ying-Ao Yang, Fei-Yang Chen, Lu-Qing Zhang, Xiao-Xiao He, Zi-Xuan He, Wei-Xiang Guo, Xiao-Juan Zhu, Hua-Li Yu
Summary: This study reveals that Dip2a gene knockout in mice induces autism-like behaviors accompanied by anxiety. Dip2a knockout leads to a reduction in dendritic length of cortical and hippocampal excitatory neurons, and the abnormality in the AMPK-mTOR signaling pathway is implicated as the underlying molecular mechanism. In addition, deletion of Dip2a in adult-born hippocampal neurons increases susceptibility to anxiety, which can be rescued by the application of mTOR inhibitor. High-fat diet intake alleviates anxiety symptoms in Dip2a knockout mice.
Article
Immunology
Qi Zuo, Zhikui Cheng, Guoqing Zhang, Yongfang Xia, Gang Xu, Wei Cao, Xiaodan Yang, Yundong Fu, Rui He, Peining Fang, Yifei Guo, Longyu Nie, Yu Huang, Lin Liu, Jianbo Zhan, Shi Liu, Ying Zhu
Summary: The study reveals that the IL-6-IL-27 complex exhibits stronger antiviral effects than individual subunits, mainly mediated by IL-27A subunit and IL-27 receptor alpha. This complex induces phosphorylation of STAT1 and STAT3, showing antiviral activity in host defense against viruses.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Cell Biology
Flavio P. Veras, Gabriel A. Publio, Bruno M. Melo, Douglas S. Prado, Thaina Norbiato, Nerry T. Cecilio, Carlos Hiroki, Luis Eduardo A. Damasceno, Rebecca Jung, Juliana E. Toller-Kawahisa, Timna Martins, Stella F. Assuncao, Diogenes Lima, Marcia G. Alves, Gabriel V. Vieira, Lucas A. Tavares, Ana L. R. Alves-Rezende, Susanne H. Karbach, Helder I. Nakaya, Thiago M. Cunha, Cacilda S. Souza, Fernando Q. Cunha, Katiuchia U. Sales, Ari Waisman, Jose C. Alves-Filho
Summary: PKM2 mediates IL-17A signaling in keratinocytes, triggering the development of skin psoriatic inflammation. PKM2 forms a complex with Act1 and TRAF6, regulating NF-KB transcriptional signaling. Additionally, IL-17 also induces PKM2 expression in keratinocytes. These findings reveal an important signaling circuit for the development of psoriasis and suggest that PKM2 may serve as a potential therapeutic target for psoriasis.
Article
Immunology
Sunkyung Kim, Jing Chen, Suin Jo, Feiya Ou, Stephen T. Ferris, Tian-Tian Liu, Ray A. Ohara, I. I. I. David A. Anderson, Renee Wu, Michael Y. Chen, William E. Gillanders, William E. Gillanders, Theresa L. Murphy, Kenneth M. Murphy
Summary: We demonstrate that tumor-derived IL-6 inhibits the development of type 1 classical dendritic cells (cDC1) by inducing C/EBPβ expression in common dendritic cell progenitors (CDPs). This leads to the upregulation of Zeb2 expression in the -165 kb enhancer, preventing the specification of pre-cDC1. Our findings explain how tumor-associated IL-6 suppresses cDC1 development and suggest that targeting abnormal C/EBPβ induction in CDPs could enhance antitumor immunity.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Surgery
Rebecca Mercieca-Bebber, Renee Eggins, Kilian Brown, Val J. Gebski, Kate Brewer, Lenna Lai, Lisa Bailey, Michael J. Solomon, John W. Lumley, Peter Hewett, Andrew D. Clouston, Kate Wilson, Wendy Hague, Julian Hayes, Stephen White, Matt Morgan, R. John Simes, Andrew R. L. Stevenson
Summary: This study aimed to compare the urinary, bowel, and sexual functioning of rectal cancer patients who underwent open or laparoscopic surgery. The results showed that patients who underwent open surgery had fewer symptoms in bowel and sexual functioning. However, it remains difficult to recommend one surgical approach over the other for rectal resection.
Article
Pathology
Vanessa Young, Andrew Clouston, Sophie Corbett-Burns, Peter Russell
INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY
(2023)
Letter
Hematology
Motoko Koyama, Luke Samson, Kathleen S. Ensbey, Shuichiro Takahashi, Andrew D. Clouston, Paul J. Martin, Geoffrey R. Hill
Article
Oncology
Charlotte Lemech, Keith Dredge, Darryn Bampton, Edward Hammond, Andrew Clouston, Nigel J. Waterhouse, Amanda C. Stanley, Lucie Leveque-El Mouttie, Grace M. Chojnowski, Andrew Haydon, Nick Pavlakis, Matthew Burge, Michael P. Brown, David Goldstein
Summary: This study evaluated the safety, efficacy, and pharmacodynamics of pixatimod and nivolumab in immunologically cold cancers. The combination therapy showed some antitumor activity in the MSS mCRC cohort, indicating the need for further investigation.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Neurosciences
Stephan A. Muller, Merav D. Shmueli, Xiao Feng, Johanna Tushaus, Neele Schumacher, Ryan Clark, Brad E. Smith, An Chi, Stefan Rose-John, Matthew E. Kennedy, Stefan F. Lichtenthaler
Summary: In this study, the researchers identified SEZ6 and gp130/IL6ST as physiological substrates of BACE1 in non-human-primate cerebrospinal fluid. They also found a reduction of gp130 in human CSF from a clinical trial with a BACE inhibitor and in plasma of BACE1-deficient mice. These findings provide insights into the relationship between BACE1 and gp130 in neuronal signaling and survival.
MOLECULAR NEURODEGENERATION
(2023)
Article
Immunology
Xiaoyu Zhang, Wenrui Yang, Donglin Yang, Jialin Wei, Ping Zhang, Sizhou Feng, Erlie Jiang, Li Zhang, Yi He, Fengkui Zhang, Mingzhe Han
Summary: Hepatitis-associated aplastic anemia is a rare type of acquired aplastic anemia characterized by bone marrow failure following hepatitis. The study analyzed the outcomes of severe HAAA patients treated with immunosuppressive therapy, matched-sibling donor hematopoietic stem cell transplantation, or haploidentical-donor HSCT as the first-line treatment. The findings showed that HSCT resulted in a higher and more sustained hematologic response compared to IST. Overall survival rates were similar among the treatment groups, but HSCT demonstrated a trend of better failure-free survival rates, particularly in young patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Agatha Schwarz, Rebecca Philippsen, Serena G. Piticchio, Jan N. Hartmann, Robert Haesler, Stefan Rose-John, Thomas Schwarz
Summary: The organ-specific microbiome, particularly the skin microbiome, plays a crucial role in tissue homeostasis by regulating the inflammatory response. Short chain fatty acids (SCFA) induce regulatory T cells (Treg) in the skin and their signal is mediated by the receptor HCA2. Knock-out of HCA2 results in stronger inflammation and a switch of Treg from a suppressive to a proinflammatory type, indicating that the skin microbiome dictates the outcome of the inflammatory reaction.
FRONTIERS IN IMMUNOLOGY
(2023)
Letter
Biophysics
Philip Wong, David C. Whiteman, Catherine M. Olsen, Yin Yuan, Jason Butler, Cameron Curley, Simon Durrant, Andrea Henden, James Morton, Elango Subramoniapillai, Caroline Stewart, Siok-Keen Tey, Glen A. Kennedy, Ashleigh P. Scott
BONE MARROW TRANSPLANTATION
(2023)
Review
Biophysics
Ashleigh P. P. Scott, Andrea Henden, Glen A. A. Kennedy, Siok-Keen Tey
Summary: Acute gastrointestinal graft versus host disease (GI-GVHD) is a serious complication of allogeneic haematopoietic cell transplantation (HCT) with limited diagnostic methods. Innovative investigations using tissue-based biomarker assessment and molecular imaging by positron emission tomography (PET) have the potential to accurately guide GI-GVHD management. This article reviews the evidence regarding GI-GVHD diagnosis and explores the evolving role of PET in predicting or diagnosing GI-GVHD.
BONE MARROW TRANSPLANTATION
(2023)
Article
Immunology
Motoko Koyama, Daniel S. Hippe, Sujatha Srinivasan, Sean C. Proll, Oriana Miltiadous, Naisi Li, Ping Zhang, Kathleen S. Ensbey, Noah G. Hoffman, Christine R. Schmidt, Albert C. Yeh, Simone A. Minnie, Susan M. Strenk, Tina L. Fiedler, Namita Hattangady, Jacob Kowalsky, Willian M. Grady, Mariapia A. Degli-Esposti, Antiopi Varelias, Andrew D. Clouston, Marcel R. M. van den Brink, Neelendu Dey, Timothy W. Randolph, Kate A. Markey, David N. Fredricks, Geoffrey R. Hill
Summary: Acute graft-versus-host disease (aGVHD) is a major limitation of allogeneic stem cell transplantation (SCT), and severe intestinal manifestation is the leading cause of early mortality. Intestinal microbiota control MHC class II (MHC-II) expression by ileal intestinal epithelial cells (IECs), promoting GVHD. This study showed that genetically identical mice from different vendors had different intestinal microbiota and MHC-II expression levels, resulting in varying severity of GVHD.
Article
Medicine, General & Internal
Anthony J. Deacon, Naeman N. Goetz, Nicholas Weber, Andrew Clouston, Enoka Gonsalkorala, Catherine Baskerville, Barbara Leggett
Summary: Hematological malignancies can cause liver dysfunction through various mechanisms, and paraneoplastic hepatitis is an extremely rare presentation. We present a case of paraneoplastic hepatitis caused by nodular lymphocyte-predominant Hodgkin lymphoma, which improved after treatment.
JOURNAL OF MEDICAL CASE REPORTS
(2023)
Article
Medicine, Research & Experimental
Chelsea L. Edwards, Susanna S. Ng, Fabian de Labastida Rivera, Dillon Corvino, Jessica A. Engel, Marcela Montes de Oca, Luzia Bukali, Teija C. M. Frame, Patrick T. Bunn, Shashi Bhushan Chauhan, Siddharth Sankar Singh, Yulin Wang, Jinrui Na, Fiona H. Amante, Jessica R. Loughland, Megan S. F. Soon, Nicola Waddell, Pamela Mukhopadhay, Lambros T. Koufariotis, Rebecca L. Johnston, Jason S. Lee, Rachel Kuns, Ping Zhang, Michelle J. Boyle, Geoffrey R. Hill, James S. McCarthy, Rajiv Kumar, Christian R. Engwerda
Summary: Control of malaria requires Th1 cells with IL-10 to mitigate inflammation, but IL-10+Tr1 cells can also promote parasite persistence or impair immunity. Molecular and phenotypic signatures distinguish IL-10-Th1 cells from IL-10+Tr1 cells in malaria-infected individuals and mice, and a conserved Tr1 cell signature is found in patients with malaria, dengue, and graft-versus-host disease.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Review
Immunology
Stefan Rose-John, Brendan J. Jenkins, Christoph Garbers, Jens M. Moll, Juergen Scheller
Summary: This review discusses the discovery of the IL-6 trans-signalling pathway and the development of biologics that specifically inhibit this pathway. Targeting IL-6 trans-signalling can decrease disease-promoting activities of IL-6 without blocking its protective actions.
NATURE REVIEWS IMMUNOLOGY
(2023)
Article
Medicine, Research & Experimental
Simone A. Minnie, Olivia G. Waltner, Kathleen S. Ensbey, Stuart D. Olver, Alika D. Collinge, David P. Sester, Christine R. Schmidt, Samuel R. W. Legg, Shuichiro Takahashi, Nicole S. Nemychenkov, Tomoko Sekiguchi, Gregory Driessens, Ping Zhang, Motoko Koyama, Andrew Spencer, Leona A. Holmberg, Scott N. Furlan, Antiopi Varelias, Geoffrey R. Hill
Summary: Autologous stem cell transplantation (ASCT) with lenalidomide maintenance is a standard treatment for multiple myeloma. However, most patients eventually relapse, suggesting immune escape. This study shows that TIGIT is highly expressed on activated CD8+ T cells in mobilized peripheral blood stem cell grafts, and that targeting TIGIT in combination with lenalidomide can enhance antimyeloma efficacy and improve immune phenotypes.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
