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

•Toll-like receptors mediate interactions between environmental stimuli and innate immunity.•TLRs play a crucial role in the development of acute pancreatitis and SIRS.•TLR2, TLR4, TLR7 and TLR9 are involved in type 1 and 2 diabetes mellitus.•TLRs promote pancreatic carcinogenesis and epithelial–mesenchymal transition.•TLRs represent a promising target for pancreatitis, diabetes and pancreatic cancer.

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.