학술논문
B cell-intrinsic Myd88 regulates disease progression in murine lupus.
Document Type
Academic Journal
Author
Tilstra JS; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Lupus Center of Excellence, University of Pittsburgh School of Medicine , Pittsburgh, PA, USA.; Kim M; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Gordon RA; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Leibler C; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Cosgrove HA; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Bastacky S; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Nickerson KM; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Shlomchik MJ; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Source
Publisher: Rockefeller University Press Country of Publication: United States NLM ID: 2985109R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1540-9538 (Electronic) Linking ISSN: 00221007 NLM ISO Abbreviation: J Exp Med Subsets: MEDLINE
Subject
Language
English
Abstract
Nucleic acid-specific Toll-like receptors (TLRs) have been implicated in promoting disease pathogenesis in systemic lupus erythematosus (SLE). Whether such TLRs mediate disease onset, progression, or both remains undefined; yet the answer to this question has important therapeutic implications. MyD88 is an essential adaptor that acts downstream of IL-1 family receptors and most TLRs. Both global and B cell-specific Myd88 deficiency ameliorated disease in lupus-prone mice when constitutively deleted. To address whether Myd88 was needed to sustain ongoing disease, we induced B cell-specific deletion of Myd88 after disease onset in MRL.Faslpr mice using an inducible Cre recombinase. B cell-specific deletion of Myd88 starting after disease onset resulted in ameliorated glomerulonephritis and interstitial inflammation. Additionally, treated mice had reduced autoantibody formation and an altered B cell compartment with reduced ABC and plasmablast numbers. These experiments demonstrate the role of MyD88 in B cells to sustain disease in murine lupus. Therefore, targeting MyD88 or its upstream activators may be a viable therapeutic option in SLE.
(© 2023 Tilstra et al.)
(© 2023 Tilstra et al.)