B cell-intrinsic Myd88 regulates disease progression in murine lupus.
J Exp Med
; 220(12)2023 12 04.
Article
em En
| MEDLINE
| ID: mdl-37787782
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fator 88 de Diferenciação Mieloide
/
Lúpus Eritematoso Sistêmico
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article