Figure adapted from Patra MC and Choi S. Molecules. 2016;21(11):pii:E1529; Chaudhary D, et al. J Med Chem. 2015;58(1):96-110; and O'Neill L. lmmunol Rev. 2008;226:10-18.
- The Toll-like and interleukin-1 receptors are primary mediators of innate immunity4,5
- Activation of these receptors by endogenous ligands can result in increased expression of proinflammatory cytokines such as tumor necrosis factor α and IL-8, thus triggering the inflammatory responses10-13
- In mice with genetically deleted IRAK4, the TLR/IL-1 signaling is severely impaired, suggesting that IRAK4 plays a key role in innate immunity.1 Humans with mutations in the IRAK4 gene have impaired innate and acquired immunity and may be susceptible to clinically important recurrent infections1,2,14,15
- Toll-like receptor activity is increased in rheumatoid arthritis; increased TLR signaling and IRAK4 activation may explain the pathogenesis and progression of this disease4,5,11