Article
Medicine, Research & Experimental
Sana Siddiqui, Kristina Johansson, Alex Joo, Luke R. Bonser, Kyung Duk Koh, Olivier Le Tonqueze, Samaneh Bolourchi, Rodriel A. Bautista, Lorna Zlock, Theodore L. Roth, Alexander Marson, Nirav R. Bhakta, K. Mark Ansel, Walter E. Finkbeiner, David J. Erle, Prescott G. Woodruff
Summary: The study identifies miR-141 as a key regulator of pathological airway mucus production induced by IL-13, with disruption leading to decreased goblet cell frequency and reduced mucus secretion. This miRNA may offer a novel therapeutic target for airway diseases.
Article
Immunology
Rodolfo Soria-Castro, Angel R. Alfaro-Doblado, Gloria Rodriguez-Lopez, Marcia Campillo-Navarro, Yatsiri G. Meneses-Preza, Adrian Galan-Salinas, Violeta Alvarez-Jimenez, Juan C. Yam-Puc, Rosario Munguia-Fuentes, Adriana Dominguez-Flores, Sergio Estrada-Parra, Sonia M. Perez-Tapia, Alma D. Chavez-Blanco, Rommel Chacon-Salinas
Summary: The study found that MC infected with L.m were able to clear the bacterial load and responded by degranulating and producing various cytokines. TLR2 was shown to mediate some MC activation pathways during L.m infection, particularly those related to IL-6 and IL-13 production. Interestingly, p38 activation depended on TLR2, but not ERK or NF-kappa B activation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Eva Conde, Romain Bertrand, Bianca Balbino, Jonathan Bonnefoy, Julien Stackowicz, Noemie Caillot, Fabien Colaone, Samir Hamdi, Raissa Houmadi, Alexia Loste, Jasper B. J. Kamphuis, Francois Huetz, Laurent Guilleminault, Nicolas Gaudenzio, Aurelie Mougel, David Hardy, John N. Snouwaert, Beverly H. Koller, Vincent Serra, Pierre Bruhns, Geraldine Grouard-Vogel, Laurent L. Reber
Summary: The study developed vaccines targeting IL-4 and IL-13, demonstrating promising prophylactic and therapeutic effects in mouse models of asthma. Vaccines specific for human IL-4 and IL-13 also showed efficient neutralization of these cytokines in mice, suggesting a potential long-term therapeutic strategy for allergic asthma.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Qinglan Wang, So Yeon Kim, Hiroshi Matsushita, Zhijun Wang, Vijay Pandyarajan, Michitaka Matsuda, Koichiro Ohashi, Takashi Tsuchiya, Yoon Seok Roh, Calvin Kiani, Yutong Zhao, Michael Chan, Suzanne Devkota, Shelly C. Lu, Tomoko Hayashi, Dennis A. Carson, Ekihiro Seki
Summary: TLR7 signaling has a protective effect in the AH mouse model, and the TLR7 agonistic agent 1Z1 holds therapeutic potential for the treatment of ALD. Oral administration of 1Z1 prevents intestinal barrier disruption and bacterial translocation, suppressing ethanol-induced hepatic injury, steatosis, and inflammation. 1Z1 treatment also up-regulates the expression of antimicrobial peptides and intestinal IL-22, modulating the microbiome composition and playing a protective role in the AH mouse model.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Medicine, Research & Experimental
Aekkacha Moonwiriyakit, Chantapol Yimnual, Rattikarn Noitem, Sasiwimol Dinsuwannakol, Jenjira Sontikun, Suchada Kaewin, Nichakorn Worakajit, Virawudh Soontornniyomkij, Chatchai Muanprasat
Summary: The activation of GPR120 can alleviate allergic inflammation and airway epithelial remodeling through the inhibition of STAT6 and Akt, suggesting that GPR120 may represent a novel therapeutic target for diseases associated with airway epithelial remodeling, including asthma.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Immunology
Walter V. Velasco, Nasim Khosravi, Susana Castro-Pando, Nelly Torres-Garza, Maria T. Grimaldo, Avantika Krishna, Michael J. Clowers, Misha Umer, Sabah Tariq Amir, Diana Del Bosque, Soudabeh Daliri, Maria Miguelina de la Garza, Marco Ramos-Castaneda, Scott E. Evans, Seyed Javad Moghaddam
Summary: By knocking out TLR2, 4, and 9 genes, we found that TLRs play an important role in the promotion of K-ras-driven lung adenocarcinoma by COPD-like airway inflammation caused by prolonged exposure to pathogenic foreign antigens in airway epithelial cells. Knockout of TLR2, 4, or 9 resulted in reduced tumor burden, angiogenesis, and tumor cell proliferation, accompanied by increased tumor cell apoptosis and reprogramming of the tumor microenvironment to an antitumorigenic state. Knocking out downstream signaling pathways, MyD88/NF-kappa B, in airway epithelial cells further confirmed these findings. Our study expands the understanding of TLR signaling in lung cancer and may contribute to the development of more reliable and effective prevention and treatment modalities for lung cancer.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Gastroenterology & Hepatology
Michael Brusilovsky, Mark Rochman, Tetsuo Shoda, Michael Kotliar, Julie M. Caldwell, Lydia E. Mack, John A. Besse, Xiaoting Chen, Matthew T. Weirauch, Artem Barski, Marc E. Rothenberg
Summary: This study identifies vitamin D as a natural IL-13 antagonist that can regulate the functions of the esophageal epithelial barrier, providing a novel therapeutic approach for type 2 immunity-related diseases.
Article
Allergy
Maya E. Kotas, Neil N. Patel, Emily K. Cope, Jose G. Gurrola II, Andrew N. Goldberg, Steven D. Pletcher, Max A. Seibold, Camille M. Moore, Erin D. Gordon
Summary: This study reveals that IL-13-induced epithelial remodeling is characterized by alterations in cell types and prostaglandin E2 stimulation in nasal polyposis, while IL-17 signaling is more prominent in CRS without polyps. Clinical severity correlates with the degree of IL-13-driven epithelial remodeling.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Review
Critical Care Medicine
Sahil Gupta, James N. Tsoporis, Song-Hui Jia, Claudia C. dos Santos, Thomas G. Parker, John C. Marshall
Summary: This article discusses how host cells recognize danger signals using pattern recognition receptors, focusing on Toll-like receptors (TLRs) as the most studied class of PRRs. It reviews the expression, regulation, and function of different TLRs, emphasizing TLR-4, and how TLR adaptor protein binding directs intracellular signaling to activate or terminate an innate immune response. The recent progress in research on the involvement of S100 proteins as ligands for TLR-4 in inflammatory disease is also highlighted.
Article
Biochemistry & Molecular Biology
Yuchen Feng, Shengchong Chen, Luyang Xiong, Chenli Chang, Wenliang Wu, Dian Chen, Jiali Gao, Gongqi Chen, Lingling Yi, Guohua Zhen
Summary: CDH26 serves as a key regulator of epithelial IL-4R signaling in asthma, playing a role in airway hyperresponsiveness, mucus overproduction, and eosinophilia. It modulates IL-4R signaling by regulating IL-13 binding, IL-4R alpha expression, and downstream phosphorylation of Jak1 and Stat6. CDH26 may serve as a potential therapeutic target for IL-4R-mediated allergic diseases.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Immunology
Song Xiao, Zhiping Lu, Martin Steinhoff, Yanqing Li, Timo Buhl, Michael Fischer, Weiwei Chen, Wenke Cheng, Renkai Zhu, Xinrong Yan, Hua Yang, Yang Liu, Yu Dou, Wanzhi Wang, Jiafu Wang, Jianghui Meng
Summary: The study revealed an upregulated expression of IL-13Rα-2 in the skin of AD patients, but not in psoriasis patients, in a disease activity-dependent manner. IL-13 was found to regulate keratinocyte-derived IL-13Rα-2 and TLR2 to modulate neuronal IL-13Rα-2, promoting neurogenic inflammation and exacerbating AD and itch. Hence, the IL-13-IL-13Rα-2 pathway and the neuronal TLR2-IL-13Rα-2 pathway are potential targets for treating AD and itch.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Article
Biochemistry & Molecular Biology
Mei-Lan Tsai, Ming-Kai Tsai, Yi-Giien Tsai, Yu-Chih Lin, Ya-Ling Hsu, Yi-Ting Chen, Yi-Ching Lin, Chih-Hsing Hung
Summary: This study investigated the effects of LTRAs on the expression of epithelium-derived cytokines in human airway epithelial cells and explored the underlying intracellular processes, including epigenetic regulation. It was found that LTRAs might induce the production of IL-25, IL-33, and TSLP by activating the MAPK and NF-kappa B pathways and regulating histone H3 acetylation and H3K36 and H3K79 trimethylation, exacerbating inflammation and asthma symptoms. Therefore, LTRA monotherapy may not be an appropriate therapeutic option for asthma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Axel Dietschmann, Sebastian Schruefer, Stefanie Westermann, Fiona Henkel, Kirstin Castiglione, Ralf Willebrand, Jasmin Adam, Jurgen Ruland, Roland Lang, Donald C. Sheppard, Julia Esser-von-Bieren, Daniel Radtke, Sven Krappmann, David Voehringer
Summary: Eosinophilia is associated with various inflammatory diseases, such as allergic bronchopulmonary aspergillosis (ABPA). It has been shown that direct interaction between eosinophils and Aspergillus fumigatus is essential for the activation of eosinophils, which then secrete multiple proinflammatory mediators. The PI3K-AKT-mTOR pathway plays a crucial role in A. fumigatus-induced eosinophil activation.
Article
Biochemistry & Molecular Biology
Rana Al-Sadi, Viszwapriya Dharmaprakash, Prashant Nighot, Shuhong Guo, Meghali Nighot, Toan Do, Thomas Y. Ma
Summary: The probiotic bacteria BB1 causes a strain-specific enhancement of the intestinal TJ barrier through a novel mechanism involving BB1 attachment to the enterocyte TLR-2 receptor complex and activation of p38 kinase pathway. This enhancement is sustained, and BB1 strain designated as BB1 causes a maximal enhancement in TJ barrier function. The mechanism of BB1 enhancement of intestinal TJ barrier is mediated by the p38 kinase pathway, not the NF-kappa B signaling pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Gastroenterology & Hepatology
Jan Raabe, Kim M. Kaiser, Michael ToVinh, Claudia Finnemann, Philipp Lutz, Christoph Hoffmeister, Jenny Bischoff, Felix Goeser, Dominik J. Kaczmarek, Tim R. Glowka, Steffen Manekeller, Arthur Charpentier, Bettina Langhans, Hans Dieter Nischalke, Marieta Toma, Christian P. Strassburg, Ulrich Spengler, Ali T. Abdallah, Benjamin Kramer, Jacob Nattermann
Summary: In this study, researchers performed a detailed characterization of intrahepatic innate lymphoid cells (ILCs) in healthy and fibrotic livers, and identified a previously undescribed subset of ILC3-like cells that produce IL-13. These cells were enriched in human liver and increased in fibrotic livers. IL-13 production by ILC3 induced proinflammatory gene upregulation in hepatic stellate cells, suggesting a potential role in the modulation of chronic liver disease.