The role of toll-like receptors in diabetic kidney disease.

PURPOSE OF REVIEW: Involved in innate immunity, toll-like receptors (TLRs) recognize pathogenic and endogenous ligands. Ligand binding initiates an inflammatory cascade which if sustained leads to fibrosis. This review summarizes the role of TLRs in diabetic kidney disease (DKD) with particular emphasis on TLR2 and TLR4.

RECENT FINDINGS: Collectively, preclinical evidence to date supports the causative role of TLR2 and TLR4 in both type I and type II DKD. The relative importance of each is still unclear. In experimental models, there are increased TLR2 and TLR4 ligands, expression and signalling. Functional studies using inhibitors or knockout animal models confirm causality. Clinical evidence also supports increased ligands and TLR2 and TLR4 expression in diabetes however there are no clinical studies examining whether interruption of these pathways confer renoprotection.

SUMMARY: Preclinical evidence to date supports the role of TLR2 and TLR4 in DKD. It will be useful to examine the value of interrupting these signalling pathways in clinical trials.