Article
Nutrition & Dietetics
Liming Liu, Fengyuan Li, Tuo Shao, Lihua Zhang, Jiyeon Lee, Gerald Dryden, Craig J. McClain, Cuiqing Zhao, Wenke Feng
Summary: This study found that fibroblast growth factor 21 (FGF21) can be induced by inflammatory stimuli. Using an experimental model of inflammatory bowel disease (IBD), the researchers discovered that FGF21 deficiency can attenuate the severity of the disease. The attenuation is likely mediated by enhancing the activation of the IL-22-STAT3 signaling pathway in intestinal epithelial cells.
Review
Immunology
Hannes Lindahl, Tomas Olsson
Summary: IL-22 is a significant interleukin that plays a crucial role in the immune system and tissue repair, particularly in T cell-driven inflammatory diseases. Its influence on T cells has not been fully understood so far, and further research is needed to explore its role in promoting regulatory T cell responses.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Microbiology
Kunyu Zhang, Lei Chen, Chenyu Zhu, Meng Zhang, Chaozhao Liang
Summary: T helper 22 (Th22) cells, characterized by their distinct cytokine profile, play variable roles in human immunity. The main effector molecule secreted by Th22 cells is IL-22, which has both protective and deleterious effects on infectious diseases. Th22/IL-22 may be a promising therapeutic target and an effective treatment strategy for various infections.
Article
Biotechnology & Applied Microbiology
Jia Zhang, Zhou Liu, Lingpeng Liu, Mingwen Huang, Yong Huang
Summary: T helper cell 22 (Th22) and its main cytokine interleukin 22 (IL-22) play a crucial role in the progression of Hepatitis B Virus-related hepatocellular carcinoma (HCC). In this study, it was found that Th22 cells promoted the proliferation and inhibited the apoptosis of HCC cells. Furthermore, the overexpression of IL-22 triggered the over-activation of STAT3, leading to the progression of HCC.
Article
Pharmacology & Pharmacy
Huimin Lai, Zhengbiao Yang, Zhaohuan Lou, Feng Li, Feng Xie, Wei Pan, Cong Xu, Lili Zhang, Sheng Zhang, Lijiang Zhang, Mincong Huang
Summary: The root extract of Lindera aggregata can effectively treat ulcerative colitis by inhibiting IL-6 production and secretion, regulating the IL-6/STAT3 signaling pathway, and modulating the balance of Th17 and Treg cells.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Viva J. Rase, Reid Hayward, James M. Haughian, Nicholas A. Pullen
Summary: Immunotherapies relying on type 1 immunity have shown limited effectiveness in solid breast tumors. This study investigated the role of type 3 immunity in breast cancer and found that IL-6 depletion combined with immunotherapy could improve outcomes by expanding T(h)17 cell populations and reducing T(h)22 cells and MDSC. This suggests that targeting IL-6 could be a potential strategy to overcome immunotherapy resistance in breast cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Wenzhe Zhang, Shiru Xu, Rongrong Zhang, Zhuqing Li, Nianyu Li, Xiruo Zhang, Yueshuang Lu, Yuehong Bian, Ping Yang, Fang Fang, Yingying Qin, Xue Jiao
Summary: This study found that deficiency of IL-22 was associated with premature ovarian insufficiency (POI). The levels of IL-22 and IL-22BP were measured and compared among different groups, and it was discovered that IL-22 levels were significantly lower in the POI group. The study also identified a correlation between IL-22 and ovarian reserve markers, providing new insights into the autoimmune disturbance in POI and suggesting potential intervention strategies.
AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
(2023)
Article
Plant Sciences
Yaxing Zhao, Haofan Luan, Hua Jiang, Yingmei Xu, Xiaojun Wu, Yubin Zhang, Ruiyan Li
Summary: The study demonstrated that Gegen Qinlian decoction (GQ) alleviated symptoms of ulcerative colitis (UC) in mice by modulating immune imbalance, reducing the production of inflammatory factors, improving dysregulation of Treg and Th17 cells, and suppressing IL-6/JAK2/STAT3 signaling pathway.
Article
Chemistry, Medicinal
Yao-Jun Liu, Wei-Heng Xu, Li-Ming Fan, Yu-Qin Zhang, Wen Xu, Ya-Ping Chen, Lin-Lin Chen, Li Chen, Wei Xu, Yan Wang, Ke-Dan Chu, Jun-Ping Zhang
Summary: This study found that polydatin can inhibit the differentiation of Th17 cells and alleviate inflammatory bowel disease. By inhibiting the phosphorylation of STAT3, polydatin reduces the number of Th17 cells and relieves colitis.
PHYTOTHERAPY RESEARCH
(2022)
Article
Multidisciplinary Sciences
Hung-Yu Chiang, Hsueh-Han Lu, Janaki N. Sudhakar, Yu-Wen Chen, Nien-Shin Shih, Yi-Ting Weng, Jr-Wen Shui
Summary: IL-22 induces IL-18 expression by intestinal epithelial cells, and IL-18 plays an important role in host defense against intestinal infection and inflammation.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Christopher Sie, Ravi Kant, Christian Peter, Andreas Muschaweckh, Monika Pfaller, Lucy Nirschl, Helena Dominguez Moreno, Tereza Chadimova, Gildas Lepennetier, Tanja Kuhlmann, Rupert Ollinger, Thomas Engleitner, Roland Rad, Thomas Korn
Summary: Th17 cells have an intrinsic feedback mechanism to control their pathogenicity, involving the production of IL-24 and secretion of IL-10. IL-24 interacts with Grim19 on the inner mitochondrial membrane to promote STAT3 accumulation in the mitochondrial compartment, which serves as a rheostat to regulate nuclear STAT3 activity. This mechanism plays an important role in restricting immunopathology associated with Th17 cells.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Qianwen Peng, Ting Pan, Ruirui He, Ming Yi, Lingyun Feng, Zhihui Cui, Ru Gao, Heping Wang, Xiong Feng, Hui Li, Yuan Wang, Cun-jin Zhang, Du Cheng, Yanyun Du, Chenhui Wang
Summary: This study reveals that BTNL2 is necessary for colorectal IL-22 production and its knockout leads to decreased colonic tumorigenesis and more severe colitis phenotypes. BTNL2 acts on ILC3s, CD4(+) T cells, and gamma delta T cells to promote IL-22 production. Importantly, a monoclonal antibody against BTNL2 attenuates colorectal tumorigenesis in mice and mBTNL2-Fc recombinant protein shows therapeutic effect in a colitis model. This study not only identifies a regulatory mechanism of IL-22 production in the colorectal system, but also provides a potential therapeutic target for human colorectal cancer and inflammatory bowel diseases.
Article
Multidisciplinary Sciences
Shengzhang Dong, George Dimopoulos
Summary: Ae. aegypti mosquitoes play a crucial role in transmitting important human viral diseases. The disruption of the siRNA pathway by CRISPR/Cas9-mediated Ago2 knockout impairs the mosquitoes' ability to degrade arbovirus RNA, leading to hyper-infection, cell lysis, tissue damage, and ultimately mosquito death.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Dino Gobelli, Pablo Serrano-Lorenzo, Maria J. Esteban-Amo, Julia Serna, M. Teresa Perez-Garcia, Antonio Orduna, Alexis A. Jourdain, Miguel A. Martin-Casanueva, Miguel A. . de la Fuente, Maria Simarro
Summary: The subunits Sdha and Sdhb of the mitochondrial electron transport chain play important roles in the respiration and effector responses of macrophages. Their absence impairs the stabilization of HIF-1 alpha and the production of the pro-inflammatory cytokine IL-1 beta in response to LPS stimulation, and also inhibits the production of IL-10. This is due to the excessive accumulation of mitochondrial reactive oxygen species (mitoROS) and the inhibition of Stat3 tyrosine phosphorylation caused by the absence of Sdha and Sdhb.
Article
Multidisciplinary Sciences
Wanzhen Li, Hongxin Jiang, Chen Bai, Shuna Yu, Yitong Pan, Chenchen Wang, Huiting Li, Ming Li, Yaxin Sheng, Fangfang Chu, Jie Wang, Yuting Chen, Jianguo Li, Jiying Jiang
Summary: This study found that Ac2-26 could alleviate HIRI by inhibiting the activation of the IL-22/IL-22R1/STAT3 signaling pathway. Ac2-26 reduced oxidative stress and inhibited the mitochondrial apoptosis pathway, leading to improved liver function, reduced cell apoptosis, and alleviated inflammation.
Editorial Material
Gastroenterology & Hepatology
Jay Vasant Patankar, Mircea Teodor Chiriac, Malte Lehmann, Anja A. Kuehl, Raja Atreya, Christoph Becker
Article
Gastroenterology & Hepatology
Daniela Regensburger, Clara Tenkerian, Victoria Puerzer, Benjamin Schmid, Thomas Wohlfahrt, Iris Stolzer, Rocio Lopez-Posadas, Claudia Guenther, Maximilian J. Waldner, Christoph Becker, Heinrich Sticht, Katja Petter, Christian Flierl, Tobias Gass, Tim Thoenissen, Carol Geppert, Nathalie Britzen-Laurent, Valerie S. Meniel, Andreas Ramming, Michael Stuerzl, Elisabeth Naschberger
Summary: This study reveals that SPARCL1 inhibits angiogenesis, supports vessel morphogenesis and integrity, and has anti-inflammatory properties. The acidic domain of SPARCL1 is identified as necessary for its anti-angiogenic activity.
INFLAMMATORY BOWEL DISEASES
(2021)
Article
Gastroenterology & Hepatology
Moritz Leppkes, Aylin Lindemann, Stefanie Goesswein, Susanne Paulus, Dominik Roth, Anne Hartung, Eva Liebing, Sebastian Zundler, Miguel Gonzalez-Acera, Jay Patankar, Fabrizio Mascia, Kristina Scheibe, Markus Hoffmann, Stefan Uderhardt, Christine Schauer, Sebastian Foersch, Clemens Neufert, Michael Vieth, Georg Schett, Raja Atreya, Anja A. Kuehl, Andre Bleich, Christoph Becker, Martin Herrmann, Markus F. Neurath
Summary: Bleeding ulcers and erosions are common in active ulcerative colitis, with fibrin layers correlated with rectal bleeding. Neutrophils induce secondary immunothrombosis through PAD4-dependent mechanisms, protecting against acute colitis and rectal bleeding. Deficiency in immunothrombosis can lead to exacerbated colitis and increased bleeding.
Article
Oncology
Antonia M. Stehr, Guangxia Wang, Richard Demmler, Marc P. Stemmler, Julia Krug, Philipp Tripal, Benjamin Schmid, Carol Geppert, Arndt Hartmann, Luis E. Munoz, Janina Schoen, Simon Voelkl, Susanne Merkel, Christoph Becker, Georg Schett, Robert Gruetzmann, Elisabeth Naschberger, Martin Herrmann, Michael Stuerzl
Summary: Neutrophil extracellular traps (NETs), released by neutrophils, have been found in colorectal cancer (CRC) tissues and are associated with disease progression. This study used high-resolution microscopy to detect citrullinated NETs in colon cancer tissues and found that citrullinated NETs were significantly associated with high tumour grades and lymph node metastasis. In vitro experiments also showed that purified NETs induced filopodia formation and cell motility in CRC cell lines, indicating their potential contribution to CRC metastasis.
JOURNAL OF PATHOLOGY
(2022)
Article
Cell Biology
Yu-Qiang Yu, Veronika Thonn, Jay Patankar, Oana-Maria Thoma, Maximilian Waldner, Marta Zielinska, Li-li Bao, Miguel Gonzalez-Acera, Stefan Wallmueller, Felix B. Engel, Michael Stuerzl, Markus F. Neurath, Eva Liebing, Christoph Becker
Summary: This study reveals that SMYD2 is overexpressed in colorectal cancer and plays a crucial role in tumor growth while inhibiting TNF-induced apoptosis and necroptosis.
CELL DEATH & DISEASE
(2022)
Review
Cell Biology
Raman Preet Kaur Gill, Jennifer Gantchev, Amelia Martinez Villarreal, Brandon Ramchatesingh, Elena Netchiporouk, Oleg E. Akilov, Niels odum, Robert Gniadecki, Sergei B. Koralov, Ivan V. Litvinov
Summary: Cutaneous T-cell lymphoma (CTCL) is a group of lymphoproliferative disorders caused by the infiltration of malignant T cells into the skin. Despite the challenges in diagnosis, studying cell lines and xenograft/GEMMs is crucial for advancing our understanding of the pathogenesis of CTCL.
Article
Biology
Johanna Grinat, Frauke Kosel, Neha Goveas, Andrea Kranz, Dimitra Alexopoulou, Klaus Rajewsky, Michael Sigal, A. Francis Stewart, Julian Heuberger
Summary: This study reveals the importance of histone methyltransferase Mll1 in the control of lineage specification of intestinal secretory Paneth and goblet cells. Mll1 prevents intestinal progenitor cells from differentiation but also plays a role in the differentiation of secretory cells. Furthermore, loss of Mll1 leads to aberrant activation of Mapk signaling, which affects intestinal cell differentiation.
LIFE SCIENCE ALLIANCE
(2022)
Article
Medicine, Research & Experimental
Nathalie Tisch, Carolin Mogler, Ana Stojanovic, Robert Luck, Emilia A. Korhonen, Alexander Ellerkmann, Heike Adler, Mahak Singhal, Geza Schermann, Lena Erkert, Jay Patankar, Andromachi Karakatsani, Anna-Lena Scherr, Yaron Fuchs, Adelheid Cerwenka, Stefan Wirtz, Bruno Christian Koehler, Hellmut G. Augustin, Christoph Becker, Thomas Schmidt, Carmen Ruiz de Almodovar
Summary: This study identifies Caspase-8 as a crucial factor in maintaining vascular homeostasis in the small intestine, and its deletion leads to hemorrhages and inflammation. Furthermore, Caspase-8 appears to be particularly important in lymphatic endothelial cells for maintaining gut homeostasis. The findings highlight the active role of endothelial cell dysfunction in driving chronic small intestinal inflammation and emphasize the importance of the intestinal vasculature in safeguarding organ function.
EMBO MOLECULAR MEDICINE
(2022)
Article
Gastroenterology & Hepatology
Luz del Carmen Martinez-Sanchez, Phuong Anh Ngo, Rashmita Pradhan, Lukas-Sebastian Becker, David Boehringer, Despina Soteriou, Marketa Kubankova, Christine Schweitzer, Tatyana Koch, Veronika Thonn, Lena Erkert, Iris Stolzer, Claudia Guenther, Christoph Becker, Benno Weigmann, Monika Klewer, Christoph Daniel, Kerstin Amann, Stefan Tenzer, Raja Atreya, Martin Bergo, Cord Brakebusch, Alastair J. M. Watson, Jochen Guck, Ben Fabry, Imke Atreya, Markus F. Neurath, Rocio Lopez-Posadas
Summary: Abnormal cell shedding is associated with intestinal barrier dysfunction and inflammatory bowel diseases. Deletion of PGGTase and RAC1 in intestinal epithelial cells leads to cell overcrowding and epithelial leakage, resulting in chronic intestinal inflammation. RAC1 plays a crucial role in regulating cytoskeletal dynamics, cell mechanics, and intestinal cell shedding.
Article
Biochemical Research Methods
Lucas Kreiss, Ingo Ganzleben, Alexander Muehlberg, Paul Ritter, Dominik Schneidereit, Christoph Becker, Markus F. Neurath, Oliver Friedrich, Sebastian Schuermann, Maximilian Waldner
Summary: This study integrated Raman spectroscopy and multiphoton microscopy to investigate the biochemical composition and morphological features related to cellular components and connective tissue. The results showed significant increase in collagen levels in the fibrosis model and high correlation between autofluorescence signatures assigned to immune cells and disease severity. The study also examined the impact of integrated data sets on prediction performance in machine learning models.
JOURNAL OF BIOPHOTONICS
(2022)
Article
Multidisciplinary Sciences
Martin Hohmann, Ingo Ganzleben, Alexander Gruenberg, Jean Gonzales-Menezes, Florian Klaempfl, Benjamin Lengenfelder, Eva Liebing, Christina Heichler, Clemens Neufert, Christoph Becker, Markus F. Neurath, Maximilian J. Waldner, Michael Schmidt
Summary: This study evaluated the effectiveness of multispectral endoscopy in identifying neoplastic lesions in the colon and showed that the classification accuracy is comparable to hyperspectral endoscopy when additional spatial features are used. This supports the application of multi/hyperspectral endoscopy in clinical settings and addresses the challenges of transferring results from ex vivo to in vivo endoscopy.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Yu-Qiang Yu, Alexandra Herrmann, Veronika Thonn, Arne Cordsmeier, Markus F. Neurath, Armin Ensser, Christoph Becker
Summary: This study demonstrates that deficiency or inhibition of the cellular lysine-methyltransferase SMYD2 can decrease TMPRSS2 expression and effectively inhibit SARS-CoV-2 replication. Targeting cellular SMYD2 could be a promising tool for controlling COVID-19 infection.
Article
Multidisciplinary Sciences
Ngoc Tung Tran, Eric Danner, Xun Li, Robin Graf, Mikhail Lebedin, Kathrin de la Rosa, Ralf Kuehn, Klaus Rajewsky, Van Trung Chu
Summary: This study establishes a spacer-nick gene correction approach that combines Cas9D10A nickase with a pair of PAM-out sgRNAs, resulting in efficient gene correction with reduced off-target mutations. The results suggest that this approach provides improved safety and suitability for gene therapy.
Article
Multidisciplinary Sciences
Angelika Schmalzl, Tamara Leupold, Lucas Kreiss, Maximilian Waldner, Sebastian Schuermann, Markus F. Neurath, Christoph Becker, Stefan Wirtz
Summary: IRF-1 is a transcription factor that plays a crucial role in regulating the accumulation of intestinal ILC3s and the production of effector cytokines. It is upregulated during infection to prevent pathogen dissemination and promote the release of protective cytokine IL-22. IRF-1 also allows ILC3s to physiologically respond to IL-23 stimulation by controlling their numbers and activation.
NATURE COMMUNICATIONS
(2022)
Editorial Material
Gastroenterology & Hepatology
Christoph Becker, Timon Erik Adolph