The skin is constantly subjected to environmental insults (microbial, chemical and physical) that may trigger immune responses 20. It has been proposed that the presence of NLRP3 in the skin (keratinocytes and tissue resident dendritic cells) provides a first line of defence by enabling the rapid sensing of invading pathogens, thereby triggering an innate immune response via NLRP3 inflammasome activation 21, 22. Sensitising allergens that penetrate the skin surface induce a delayed type hypersensitivity reaction, called contact hypersensitivity (CHS) 23, 24. Evidence has been presented for the involvement of NOD-like receptors (NLR) as well as IL-1β,
IL-18 and caspase-1 in the mouse CHS
model 25, 26. Recent work has also suggested that IL-18 plays an important role by distinguishing the presence find more of contact allergens from irritants 27 (Table 1). The outcome of skin immune responses with respect to tolerance or immunity is dependent on skin NLRP3 inflammasome activation, and secreted IL-1β and IL-18 may regulate the quality of an allergen-specific Dabrafenib T-cell response in CHS 25. Furthermore, mice deficient in IL-1β have impaired CHS to trinitrochlorobenzone 28. These discoveries suggest that modulation of the NLRP3 inflammasome may offer a therapeutic strategy to modulate T-cell responses in patients suffering from allergic CHS. Excitingly, manipulation of the NLRP3 inflammasome may also offer a perspective to induce tolerance towards a given contact allergen. Type 2 diabetes (T2D) occurs when beta cells in the pancreas fail to produce sufficient insulin to overcome insulin resistance. Several lines of evidence support the role of IL-1β in the pathogenesis of T2D; expression of the IL-1Ra is reduced in the pancreatic islets of these patients, with IL-1β being produced in response to high glucose concentrations,
leading to decreased cell proliferation and apoptosis 29. Larsen et al. have reported that anakinra treatment results in decreased glycated haemoglobin (HbA1c) levels and increased insulin production in T2D patients 30. An IL-1β antibody, Xoma 052, was shown to restore glycemic control in T2D patients else in a double-blind, placebo-controlled, dose-escalation study 31. In this regard, it is also relevant that glyburide, a sulphonylurea drug used to treat T2D, inhibits the NLRP3 inflammasome 32. T2D is a burgeoning global health problem and this advance in understanding the pathogenesis will offer novel therapeutic avenues in the future. Inflammation appears to provide a local environment in which many tumours flourish and IL-1β has a key role in this process 33. Inflammasome-mediated pathogen recognition 34 provides a potential, but as yet unproven, link between infection-induced inflammation and cancer.