Lichen planus: altered AIM2 and NLRP1 expression in skin lesions and defective activation in peripheral blood mononuclear cells

• Published in: Clinical and experimental dermatology Vol. 44; no. 4; pp. e89 - e95
• Main Authors: Domingues, R., Pietrobon, A. J., Carvalho, G. C., Pereira, N. Z., Pereira, N. V., Sotto, M. N., Aoki, V., Duarte, A. J. S., Sato, M. N.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.06.2019
• Subjects: Adaptor Proteins, Signal Transducing; Adult; Agonists; Apoptosis Regulatory Proteins; ATP; Dermis; DNA-Binding Proteins; Environmental effects; Enzyme-linked immunosorbent assay; Female; Humans; Immunity, Innate - immunology; Immunohistochemistry; Inflammasomes; Inflammasomes - genetics; Innate immunity; Interleukin-1beta - metabolism; Leukocytes (mononuclear); Leukocytes, Mononuclear - metabolism; Lichen planus; Lichen Planus - metabolism; Lichen Planus - pathology; Male; Middle Aged; Peripheral blood mononuclear cells; RNA, Messenger - genetics; Skin diseases; Skin Diseases - metabolism; Skin Diseases - pathology; TLR4 protein; TLR7 protein; Toll-Like Receptor 7; Toll-Like Receptor 8; Toll-Like Receptors; Transcription; Up-Regulation - genetics
• ISSN: 0307-6938; 1365-2230
• DOI: 10.1111/ced.13859

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.