Bruton’s tyrosine kinase (BTK) is indispensable in Neutrophils to initiate and maintain Skin Inflammation in a Model of Pemphigoid Diseases

Bruton’s tyrosine kinase (BTK) is indispensable in Neutrophils to initiate and maintain Skin Inflammation in a Model of Pemphigoid Diseases | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL British Journal of Pharmacology This is a preprint and has not been peer reviewed. Data may be preliminary. 13 February 2025 V1 Latest version Share on Bruton’s tyrosine kinase (BTK) is indispensable in Neutrophils to initiate and maintain Skin Inflammation in a Model of Pemphigoid Diseases Authors : Henning Olbrich , Paul Schilf , Sripriya Murthy , Sina Gonther , Mareike Neumann , Christoph Hammers , and Christian Sadik 0000-0001-6701-048X [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.173944849.94599549/v1 397 views 387 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Bruton’s tyrosine kinase (BTK) is essential for B cell functions. Its role in myeloid cells is less understood. More insights into its significance in myeloid cells are required to evaluate its potential as therapeutic target in the effector phase of antibody-induced autoimmune diseases when inhibiting the production of autoantibodies can suppress tissue inflammation only time delayed. Such situation can be found, e.g., in acute flares of pemphigoid diseases, a group of autoimmune blistering skin diseases. We examined the effect of neutrophil-specific Btk gene deficiency and of the BTK inhibitor ibrutinib on disease in the antibody-transfer model of bullous pemphigoid (BP)-like epidermolysis bullosa acquisita (EBA), a model solely reflecting the effector phase. We additionally investigated the effect of BTK inhibitors on responses of neutrophils relevant for autoimmune diseases in vitro. Both neutrophil-specific genetic deficiency of Btk and ibrutinib vastly protected from skin inflammation. Stimulation of murine neutrophils with immune complexes activated BTK and induced the release of leukotriene B4 (LTB4) and reactive oxygen species (ROS). Deficiency in Btk nullified LTB4 but not ROS release indicating differences in the cell signaling cascades regulating the release of LTB4 and ROS upon Fcγ receptor activation signaling. Collectively, our results indicate that skin inflammation in EBA is critically controlled by a Fcγ receptor – BTK – LTB4 axis in neutrophils. This highlights BTK as promising drug target to treat EBA and potentially other antibody-induced autoimmune disease. Supplementary Material File (figure 4.tif) Download 110.98 MB File (manuscript.pdf) Download 430.02 KB Information & Authors Information Version history V1 Version 1 13 February 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Collection British Journal of Pharmacology Keywords autoimmunity epithelium fc receptors immunopharmacology in vivo inflammation leukocyte trafficking lipoxygenase repurposing translational pharmacology Authors Affiliations Henning Olbrich University of Lübeck View all articles by this author Paul Schilf University of Luebeck Human Medicine View all articles by this author Sripriya Murthy University of Lübeck View all articles by this author Sina Gonther University of Lübeck View all articles by this author Mareike Neumann University of Lübeck View all articles by this author Christoph Hammers University of Regensburg View all articles by this author Christian Sadik 0000-0001-6701-048X [email protected] Universitat zu Lubeck Sektion Medizin View all articles by this author Metrics & Citations Metrics Article Usage 397 views 387 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Henning Olbrich, Paul Schilf, Sripriya Murthy, et al. Bruton’s tyrosine kinase (BTK) is indispensable in Neutrophils to initiate and maintain Skin Inflammation in a Model of Pemphigoid Diseases. Authorea . 13 February 2025. DOI: https://doi.org/10.22541/au.173944849.94599549/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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