Article
Biochemistry & Molecular Biology
Qinxue Li, Yayun Liu, Xin Xia, Haichen Sun, Jinhuan Gao, Quanxin Ren, Tian Zhou, Chang Ma, Jinggang Xia, Chunlin Yin
Summary: The study suggests that hyperglycemia may exacerbate the complexity of coronary atherosclerosis through activation of TBK1-HIF-1 alpha-mediated IL-17/IL-10 signaling. Therefore, TBK1 could be a novel drug therapy target for coronary heart disease complicated with diabetes mellitus.
Review
Immunology
Kingston H. G. Mills
Summary: IL-17 cytokines have both protective and pathological functions in the context of infection and autoimmunity. They promote protective immunity against pathogens but can also drive inflammatory pathology. Dysregulated IL-17 responses can contribute to immunopathology, and IL-17 is implicated in various inflammatory diseases.
NATURE REVIEWS IMMUNOLOGY
(2023)
Article
Cell Biology
Arnaud Goepfert, Carmen Barske, Sylvie Lehmann, Emmanuelle Wirth, Joschka Willemsen, Johann E. Gudjonsson, Nicole L. Ward, Mrinal K. Sarkar, Rene Hemmig, Frank Kolbinger, Jean-Michel Rondeau
Summary: Through crystallography, biophysics, and mutational studies, this research demonstrates that IL-17A, IL-17F, and IL-17A/F induce IL-17RA dimerization, leading to the formation of a 2:2:2 hexameric signaling assembly. The formation of the IL-17 signalosome potentiates IL-17-induced IL-36 gamma and CXCL1 mRNA expression in human keratinocytes compared to a dimerization-defective IL-17RA variant.
Review
Medicine, General & Internal
Kamran Ghoreschi, Anna Balato, Charlotta Enerback, Robert Sabat
Summary: Psoriasis is a chronic inflammatory disease affecting 2-3% of the global population, characterized by sharply demarcated erythematous and scaly skin lesions. The disease results from hyperproliferation and disturbed differentiation of epidermal keratinocytes provoked by immune mediators of the IL-23 and IL-17 pathway. Therapeutics targeting IL-23, IL-17, and IL-17RA have shown excellent efficacy in treating psoriasis.
Article
Rheumatology
Anella Saviano, Adel Abo Manosour, Federica Raucci, Francesco Merlino, Noemi Marigliano, Anna Schettino, Mussarat Wahid, Jenefa Begum, Andrew Filer, Julia E. Manning, Gian Marco Casillo, Marialuisa Piccolo, Maria Grazia Ferraro, Simona Marzano, Pasquale Russomanno, Rosa Bellavita, Carlo Irace, Jussara Amato, Mohammed Alfaifi, Peter Rimmer, Tariq Iqbal, Stefano Pieretti, Valentina Vellecco, Francesco Caso, Luisa Costa, Roberto Giacomelli, Raffaele Scarpa, Giuseppe Cirino, Mariarosaria Bucci, Helen M. McGettrick, Paolo Grieco, Asif Jilani Iqbal, Francesco Maione
Summary: This study identified a novel IL-17A/F-derived peptide and generated a new anti-IL-17 antibody that can effectively reverse the pro-inflammatory actions of IL-17A/F. The antibody showed less off-target effects compared to the current gold-standard biologic. Preclinical and clinical evidence demonstrated the high efficacy and therapeutic potency of the antibody in patients with IMIDs.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Editorial Material
Biochemistry & Molecular Biology
Iliyan D. Iliev, Woan-Yu Lin, Sarah L. Gaffen
Summary: Microbiota-induced IL-17 production plays a role in CNS processes and animal behavior, but its role in the PNS is not well understood. Enamorado et al. show that commensal-specific Th17 cells are activated after tissue injury to promote local nerve regeneration, which is regulated by IL-17 signaling on peripheral neurons.
Review
Immunology
Efterpi Zafiriou, Athina I. Daponte, Vasileios Siokas, Christina Tsigalou, Efthymios Dardiotis, Dimitrios P. Bogdanos
Summary: Psoriasis patients often have obesity, anxiety, or depressive disorders, with the pivotal role of IL-17 and IL-23 in the immunopathogenesis of psoriasis. Monoclonal antibodies inhibiting IL-17 and IL-23 are widely used for psoriatic disease treatment. IL-17 and its related cells play a decisive role in the induction and progression of obesity and depression, suggesting a potential interconnected manifestation between psoriatic disease, obesity, and anxiety/depression.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Endocrinology & Metabolism
Cagri Bodur, Dubek Kazyken, Kezhen Huang, Aaron Seth Tooley, Kae Won Cho, Tammy M. Barnes, Carey N. Lumeng, Martin G. Myers, Diane C. Fingar
Summary: TBK1-mTOR signaling plays a crucial role in controlling glucose metabolism and improving glycemic control during diet-induced obesity. Increased TBK1 activity and mTOR phosphorylation contribute to the attenuation of insulin resistance, leading to better glycemic control.
Article
Cell Biology
Koshiro Sonomoto, Rui Song, Daniel Eriksson, Anne M. Hahn, Xianyi Meng, Pang Lyu, Shan Cao, Ning Liu, R. Verena Taudte, Stefan Wirtz, Yoshiya Tanaka, Thomas H. Winkler, Georg Schett, Didier Soulat, Aline Bozec
Summary: This study found that only dietary fat, not carbohydrates or proteins, exacerbates psoriatic disease. High-fat diet can change the intestinal mucus layer and microbiota composition, leading to the aggravation of psoriatic skin inflammation. Changing the intestinal microbiota can effectively block the skin inflammation caused by high-fat diet, inhibit the systemic interleukin-17 (IL-17) response, and increase the population of mucophilic bacteria Akkermansia muciniphila. Oral administration of live or heat-killed A. muciniphila can effectively inhibit the enhancement of psoriatic disease caused by high-fat diet.
Editorial Material
Immunology
Stefan Bittner, Frauke Zipp
Summary: IL-17-blocking antibodies have limited clinical effect in certain autoimmune diseases. This study demonstrates that SHP2-Act1 complexes can mediate IL-17R signaling autonomously, even in the absence of the IL-17 ligand itself.
Article
Medicine, Research & Experimental
Peng Zhao, Xiaoli Sun, Zhongji Liao, Hong Yu, Dan Li, Zeyang Shen, Christopher K. Glass, Joseph L. Witztum, Alan R. Saltiel
Summary: Amlexanox has the potential to improve diet-induced hypertriglyceridemia atherogenesis through synergistic actions involving upregulation of bile acid synthesis, reduction of inflammation, and improvement of vascular dysfunction.
Article
Physiology
Ji-Su Shim, Hyun-Seung Lee, Hyuktae Kwon, Min-Hye Kim, Young-Joo Cho, Heung-Woo Park
Summary: Obesity disturbs glutamine metabolism, leading to enhanced inflammation by affecting immune cells. In this study, it was found that a high-fat diet induced airway hyperresponsiveness in obese mice by altering glutamine metabolism in macrophages and innate lymphoid cells. Moreover, plasma glutamine/glutamate ratios were higher in obese asthmatics compared to nonobese asthmatics.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2023)
Editorial Material
Microbiology
Ashira Lubkin, Michail S. Lionakis
Summary: In this study, Basso et al. elucidate the mechanism of the fungal lipase Lip2 during systemic infection with Candida albicans. They show that lipids released by Lip2 can manipulate the host's protective cytokine response, thereby enhancing fungal virulence.
CELL HOST & MICROBE
(2022)
Review
Immunology
Matteo Vecellio, Vivien Xanath Hake, Connor Davidson, Maria Cristina Carena, B. Paul Wordsworth, Carlo Selmi
Summary: Psoriatic arthritis (PsA) is a chronic inflammatory disease associated with psoriasis, with genetic predisposition playing a key role in its development. The IL-23/IL-17 axis is highlighted as important in the immunopathogenesis of PsA.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Claudia Schinocca, Chiara Rizzo, Serena Fasano, Giulia Grasso, Lidia La Barbera, Francesco Ciccia, Giuliana Guggino
Summary: IL-23 is a pro-inflammatory cytokine composed of two subunits and has a key role in protective immune response, but dysregulation can exacerbate chronic immune-mediated inflammation. Activation of the IL-23/IL-17 axis contributes to the development of various inflammatory diseases.
FRONTIERS IN IMMUNOLOGY
(2021)