Bruton's tyrosine kinase (BTK) is a cytoplasmic protein tyrosine kinase, which plays an essential role in B cell receptor (BCR) signaling (Brunner C et al. 2005). BTK has been also implicated in TLR signaling (Lee KG et al. 2012, Jefferies CA et al. 2003; Doyle SL et al. 2007). Interaction studies revealed that BTK can associate with intracellular TIR-domains of TLRs 4, 6, 8 and 9. Furthermore, BTK was found to interact with other proteins involved in TLR2/4 signaling - MyD88, MAL and IRAK-1 (Jefferies CA et al. 2003)
Loss of BTK function causes X-linked agammaglobulinemia (XLA), a rare primary immunode?ciency disease with severe defects in early B-cell development resulting in an almost complete absence of peripheral B cells and severely reduced serum levels of immunoglobulins of all classes (Väliaho J et al. 2006). Affected individuals suffer from recurrent bacterial and enteroviral infections. It remains unclear whether XLA patients have normal or impared TLR signaling functions. LPS-stimulated monocytes from XLA patients were found to produce reduced amounts of TNFalpha (Horwood NJ et al. 2003), These data contradict a study that showed enhanced amounts of TNFalpha and IL6 comparing to control cells, starting at 6 hours and extending for 48 hours (Marron TU et al. 2012). The other group reported similar expression TNFalpha upon TLR4 triggering, compared with healthy control cells (Perez de Diego R et al. 2006). Thus, the effect of BTK deficiency on TLR-mediated inflammation needs to be further clarified.