Key component of inflammasome, NLRC4, was identified in the lesional epidermis of psoriatic patients

Abstract

Inflammasomes are multimolecular complexes that control the inflammatory response. The function of inflammasomes in the pathogenesis of psoriasis is still unclear. To clarify the relationship between inflammasomes and the pathophysiology of psoriasis, and in particular, to identify molecules interacting with caspase-1, a crucial component of inflammasomes, scale extracts obtained from patients with psoriasis were immunoprecipitated with anti-caspase-1 antibody and analyzed by liquid chromatography coupled with electrospray tandem mass spectrometry (LC-MS/MS). The expression of the inflammasome component was assessed by immunohistochemical analysis and an in vitro assay. We identified several candidates for caspase-1-interacting proteins from the psoriatic scale extracts by immunoprecipitation and LC-MS/MS. Nucleotide-binding oligomerization domain-containing protein-like receptor family CARD domain-containing protein 4 (NLRC4) was the only inflammasome component among the candidates; thus, the protein is considered to be a key factor of inflammasomes in psoriasis. No inflammasome component was found in the extracts of atopic dermatitis or normal skin by LC-MS/MS. Immunohistochemical analysis demonstrated upregulation of NLRC4 in the lesional epidermis of some psoriatic patients whereas weak expression of NLRC4 was detected in the normal and non-lesional epidermis. The mRNA expression of the NLRC4 gene increased in keratinocytes at confluency, 48 h after air exposure and after the addition of 1.5 mmol/L calcium chloride. Our findings suggest that NLRC4 may be involved in the exacerbation or modification of psoriatic lesions.

Spontaneous atopic dermatitis in mice with a defective skin barrier is independent of ILC2 and mediated by IL‐1β

“…To date, we cannot rule out a role for the NLRC4 inflammasome (or NAIP‐NLRC4) that can directly recruit caspase‐1. In a recent study, NLRC4 was found in the scale extracts of psoriasis patients; however, no inflammasome components (including NLRC4) were found in atopic dermatitis patients . Inflammasome‐independent processing of IL‐1β has been observed in a variety of settings (reviewed in).…”

Innate immunity in allergy

“…The transcription of Naips is regulated by the transcription factor IRF‐8 . NLRC4 is implicated in the exacerbation of psoriatic lesions, and NLRP4 mutation is associated with exacerbation of asthma in smoking adults . Polymorphisms of NACHT‐LRR in NLRP12 and the promoter regions of NLRC4 and NLRP1 are associated with atopic dermatitis .…”

Activation of the NLRC4 inflammasome in renal tubular epithelial cell injury in diabetic nephropathy

“…It has also been confirmed that bacterial products can activate the NLRC4 inflammasome ( 12 ). Moreover, some studies ( 14 , 15 , 25 ) have observed that the NLRC4 inflammasome is involved in the occurrence of tumors, psoriasis and ulcerative colitis, indicating that the NLRC4 inflammasome plays an important role in the systemic inflammatory response and self-inflammatory diseases. The present study identified a causal link between NLRC4 inflammasome activation and RTEC injury.…”

“…Quantitatively, NLRC4 staining intensity exhibited a one-fold increase in the renal tubulointerstitium of patients with DN ( 13 ). In addition, it has been revealed that the expression of NLRC4 in intestinal epithelial cells is increased and it is involved in intestinal inflammation ( 14 , 15 ). The main aim of the present study was to examine the role of the NLRC4 inflammasome in renal tubular epithelial cell (RTEC) injury in DN.…”