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Summary: Background: Lichen planus (LP) is an inflammatory skin disease with unknown aetiology. Activation by pathogen‐associated molecular patterns or environmental stimuli may activate some components of inflammasomes that contribute to the inflammatory process in LP lesions. Aim: To characterize the inflammasomes in skin lesions and peripheral blood mononuclear cells (PBMCs) of patients with LP under Toll‐like receptor (TLR) activation. Methods: In total, 15 patients with LP and 14 healthy controls (HCs) were enrolled in the study. Inflammasome expression in skin was evaluated by real‐time PCR and immunohistochemistry, while ELISA was used to assess the production of interleukin (IL)‐1β by PBMCs under stimulation with TLR4 and TLR7/TLR8 agonists and adenosine triphosphate (ATP). Results: Compared with the levels in HC samples, increased expression of the inflammasome AIM2 was verified in both epidermal and dermal sections of LP skin lesions, whereas NLRP1 and IL‐β expression levels were enhanced in the dermis. LP skin lesion samples exhibited higher AIM2 transcript levels, similar NLRP1 levels and lower pro‐IL‐1β mRNA levels compared with HC samples. We verified that, compared with PBMCs from HC subjects, PBMCs from patients with LP produced similar amounts of IL‐1β after induction by TLR4 agonists but lower IL‐1β levels after induction by TLR7/TLR8 agonists, regardless of the addition of ATP. Conclusion: Alterations in innate immunity, such as inflammasome component expression in skin lesions and PBMCs, were observed in patients with LP. Further investigations of dysfunctional inflammasome activation and the chronic inflammatory status of LP are required. [ABSTRACT FROM AUTHOR]

Summary Immunological dysfunction has been described to occur in chronic idiopathic urticaria (CIU), most notably in association with an inflammatory process. Some pharmacological agents as statins - drugs used in hypercholesterolaemia - display a broad effect on the immune response and thus should be tested in vitro in CIU. Our main objectives were to evaluate the effects of statins on the innate and adaptive immune response in CIU. Simvastatin or lovastatin have markedly inhibited the peripheral blood mononuclear cells (PBMC) proliferative response induced by T and B cell mitogens, superantigen or recall antigen. Simvastatin arrested phytohaemaglutinin (PHA)-induced T cells at the G0/G1 phase, inhibiting T helper type 1 (Th1), Th2, interleukin (IL)-10 and IL-17A cytokine secretion in both patients and healthy control groups. Up-regulation of suppressor of cytokine signalling 3 (SOCS3) mRNA expression in PHA-stimulated PBMCs from CIU patients was not modified by simvastatin, in contrast to the enhancing effect in the control group. Statin exhibited a less efficient inhibition effect on cytokine production [IL-6 and macrophage inflammatory protein (MIP)-1α] induced by Toll-like receptor (TLR)-4, to which a statin preincubation step was required. Furthermore, statin did not affect the tumour necrosis factor (TNF)-α secretion by lipopolysaccharide (LPS)-stimulated PBMC or CD14+ cells in CIU patients. In addition, LPS-activated PBMC from CIU patients showed impaired indoleamine 2,3-dioxygenase (IDO) mRNA expression compared to healthy control, which remained at decreased levels with statin treatment. Statins exhibited a marked down-regulatory effect in T cell functions, but were not able to control TLR-4 activation in CIU patients. The unbalanced regulatory SOCS3 and IDO expressions in CIU may contribute to the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]