{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T21:19:28Z","timestamp":1793827168970,"version":"4.6.1"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T00:00:00Z","timestamp":1720396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Foundation of Flanders"},{"name":"Bijzonder Onderzoeksfonds"},{"DOI":"10.13039\/501100006401","name":"Charcot Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006401","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019771","name":"Rega Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019771","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Multiple sclerosis (MS) is a neurodegenerative, autoimmune disease that is still incurable. Nowadays, a variety of new drugs are being developed to prevent excessive inflammation and halt neurodegeneration. Among these are the inhibitors of Bruton's tyrosine kinase (BTK). Being indispensable for B cells, this enzyme became an appealing therapeutic target for autoimmune diseases. Recognizing the emerging importance of BTK in myeloid cells, we investigated the impact of upcoming BTK inhibitors on neutrophil functions. Although adaptive immunity in MS has been thoroughly studied, unanswered questions about the pathogenesis can be addressed by studying the effects of candidate MS drugs on innate immune cells such as neutrophils, previously overlooked in MS. In this study, we used 3 BTK inhibitors (evobrutinib, fenebrutinib, and tolebrutinib), and found that they reduce neutrophil activation by the bacterial peptide fMLF and the chemokine interleukin-8\/CXCL8. Furthermore, they diminished the production of reactive oxygen species and release of neutrophil extracellular traps. Additionally, the production of CXCL8 and interleukin-1\u03b2 in response to inflammatory stimuli was decreased. Inhibitory effects of the drugs on neutrophil activation were not related to toxicity. Instead, BTK inhibitors prolonged neutrophil survival in an inflammatory environment. Finally, treatment with BTK inhibitors decreased neutrophil migration toward CXCL8 in a Boyden chamber assay but not in a transendothelial setup. Also, in vivo CXCL1-induced migration was unaffected by BTK inhibitors. Collectively, this study provides novel insights into the impact of BTK inhibitors on neutrophil functions, thereby holding important implications for autoimmune or hematological diseases in which BTK is crucial.<\/jats:p>","DOI":"10.1093\/jleuko\/qiae160","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T16:56:19Z","timestamp":1720457779000},"source":"Crossref","is-referenced-by-count":14,"title":["Effect on neutrophil migration and antimicrobial functions by the Bruton's tyrosine kinase inhibitors tolebrutinib, evobrutinib, and fenebrutinib"],"prefix":"10.1093","volume":"117","author":[{"given":"Mirre","family":"De Bondt","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven , Herestraat 49, 3000 Leuven ,","place":["Belgium"]},{"name":"Neuro Immune Connections & Repair Lab, Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, Agoralaan C, 3500 Hasselt ,","place":["Belgium"]},{"name":"University MS Center, Pelt-Hasselt, Agoralaan gebouw D , 3590 Hasselt ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janne","family":"Renders","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven , Herestraat 49, 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paloma","family":"Petit de Prado","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven , Herestraat 49, 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nele","family":"Berghmans","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven , Herestraat 49, 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"No\u00ebmie","family":"P\u00f6rtner","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven , Herestraat 49, 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lotte","family":"Vanbrabant","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven , Herestraat 49, 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edvian Louise Soares","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven , Herestraat 49, 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayel","family":"Duran","sequence":"additional","affiliation":[{"name":"Neuro Immune Connections & Repair Lab, Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, Agoralaan C, 3500 Hasselt ,","place":["Belgium"]},{"name":"University MS Center, Pelt-Hasselt, Agoralaan gebouw D , 3590 Hasselt ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulien","family":"Baeten","sequence":"additional","affiliation":[{"name":"Neuro Immune Connections & Repair Lab, Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, Agoralaan C, 3500 Hasselt ,","place":["Belgium"]},{"name":"University MS Center, Pelt-Hasselt, Agoralaan gebouw D , 3590 Hasselt ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bieke","family":"Broux","sequence":"additional","affiliation":[{"name":"Neuro Immune Connections & Repair Lab, Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, Agoralaan C, 3500 Hasselt ,","place":["Belgium"]},{"name":"University MS Center, Pelt-Hasselt, Agoralaan gebouw D , 3590 Hasselt ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mieke","family":"Gouwy","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven , Herestraat 49, 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9685-6836","authenticated-orcid":false,"given":"Patrick","family":"Matthys","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven , Herestraat 49, 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Hellings","sequence":"additional","affiliation":[{"name":"Neuro Immune Connections & Repair Lab, Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, Agoralaan C, 3500 Hasselt ,","place":["Belgium"]},{"name":"University MS Center, Pelt-Hasselt, Agoralaan gebouw D , 3590 Hasselt 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