Btk inhibition treats TLR7/IFN driven murine lupus

Btk inhibition treats TLR7/IFN driven murine lupus

Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 164(2016) vom: 09. März, Seite 65-77
1. Verfasser: Bender, Andrew T (VerfasserIn)
Weitere Verfasser: Pereira, Albertina, Fu, Kai, Samy, Eileen, Wu, Yin, Liu-Bujalski, Lesley, Caldwell, Richard, Chen, Yi-Ying, Tian, Hui, Morandi, Federica, Head, Jared, Koehler, Ursula, Genest, Melinda, Okitsu, Shinji L, Xu, Daigen, Grenningloh, Roland
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2016
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Bruton's tyrosine kinase Interferon Lupus TLR7 Autoantibodies Immunosuppressive Agents Interferon Type I Protein Kinase Inhibitors mehr... TLR7 protein, human Terpenes Toll-Like Receptor 7 pristane 26HZV48DT1 Protein-Tyrosine Kinases EC 2.7.10.1 Agammaglobulinaemia Tyrosine Kinase EC 2.7.10.2 BTK protein, human Btk protein, mouse
Beschreibung
Zusammenfassung:Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Bruton's tyrosine kinase (Btk) is expressed in a variety of immune cells and previous work has demonstrated that blocking Btk is a promising strategy for treating autoimmune diseases. Herein, we utilized a tool Btk inhibitor, M7583, to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon. In BXSB-Yaa lupus mice, Btk inhibition reduced autoantibodies, nephritis, and mortality. In the pristane-induced DBA/1 lupus model, Btk inhibition suppressed arthritis, but autoantibodies and the IFN gene signature were not significantly affected; suggesting efficacy was mediated through inhibition of Fc receptors. In vitro studies using primary human macrophages revealed that Btk inhibition can block activation by immune complexes and TLR7 which contributes to tissue damage in SLE. Overall, our results provide translational insight into how Btk inhibition may provide benefit to a variety of SLE patients by affecting both BCR and FcR signaling
Beschreibung:Date Completed 18.07.2016
Date Revised 02.12.2018
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2016.01.012