Journal of autoimmunity
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Journal of autoimmunity · Jul 2018
TBK1: A key regulator and potential treatment target for interferon positive Sjögren's syndrome, systemic lupus erythematosus and systemic sclerosis.
Upregulation of type I interferons (IFN-I) is a hallmark of systemic autoimmune diseases like primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Expression of IFN-I is induced by three different receptor families: Toll-like receptors (TLRs), RIG-like receptors (RLRs) and DNA-sensing receptors (DSRs). TANK-binding kinase (TBK1) is an important signaling hub downstream of RLRs and DSRs. TBK1 activates IRF3 and IRF7, leading to IFN-I production and subsequent induction of interferon stimulated genes (ISGs). The objective of this study was to explore the potential of BX795, an inhibitor of TBK1, to downregulate IFN-I activation in pSS, SLE and SSc. ⋯ TBK1 inhibition reduced expression of ISGs in PBMCs from IFNpos patients with systemic autoimmune diseases indicating TBK1 as a potential treatment target.