B cell-intrinsic Myd88 regulates disease progression in murine lupus

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.

Automated summary

Studies have shown that MyD88 in B cells plays a crucial role in the onset and progression of lupus in mice, and its deficiency can improve disease symptoms and reduce autoantibody production. Therefore, targeting MyD88 or its upstream activators may be an effective option for treating lupus.