Research ArticleImmunology

The kinase IRAK4 promotes endosomal TLR and immune complex signaling in B cells and plasmacytoid dendritic cells

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Science Signaling  02 Jun 2020:
Vol. 13, Issue 634, eaaz1053
DOI: 10.1126/scisignal.aaz1053

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Blocking the loop in lupus

Systemic lupus erythematosus (SLE) is an autoimmune disorder that affects all major organs. Using newly developed inhibitors, mouse models, and blood and serum samples from patients and donors, Corzo et al. examined the roles of the B cell–associated kinases BTK and IRAK4 in SLE development. Whereas both kinases stimulated B cells in response to SLE autoantibodies, IRAK4 also mediated an autoinflammatory loop involving cytokine-secreting plasmacytoid dendritic cells. In mouse models of lupus, inhibiting IRAK4 activity reduced autoantibody production and suppressed the development of disease symptoms, including kidney damage that is often lethal in patients. The findings suggest that, unlike current therapies that only manage the symptoms of SLE, IRAK4 inhibitors may effectively treat the disease itself.

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