Toll like receptors and pancreatic diseases: From a pathogenetic mechanism to a therapeutic target.

Toll-like receptors (TLRs) mediate interactions between environmental stimuli and innate immunity. TLRs play a major role in the development of numerous pancreatic diseases, making these molecules attractive as potential therapeutic targets. TLR2, TLR7 and TLR9 are involved in the initiation of type 1 diabetes mellitus (T1DM), whereas TLR2 and TLR4 play a major role in the onset of type 2 diabetes mellitus (T2DM). Furthermore, TLRs cause derangements in several tumor suppressor proteins (such as p16, p21, p27, p53 and pRb), induce STAT3 activation and promote epithelial-mesenchymal transition as well as oncogene-induced senescence. In this review we will focus on the contribution of TLRs in pancreatic disease including cancer and we describe recent progress in TLR-modulation for the treatment of these patients.