Background/Purpose: Systemic lupus erythematous (SLE) is a systemic autoimmune disease with diverse etiological factors. It was well recognized that interferon (IFN) signature did the perpetration on the progress of this disease. NLRP12 (NOD-like receptor family (NLR) pyrin domain containing 12) is a pyrin containing NLR protein that we had linked its new biological function to the cross-regulation of Toll like receptor (TLRs) and Rig-I like receptor (RIG-I) pathways. NLPR12 acts as an innate immune check-point in regulating type I IFNs expression during TLRs and RIG-I activation. Therefore, we aimed to investigate the underline molecular mechanism of NLRP12 regulation and its significance in SLE patients.

Methods: PBMCs were collected from 60 SLE patients and 20 healthy donors for analysis of NLRP12 and IFN-α (IFNA) gene expression by RT-QPCR. PBMCs were applied for Chromatin immuneprecipitation (ChIP) assay and electrical mobility shift assay (EMSA) to determine the putative transcription factor that regulates NLRP12 expression. An involvement of epigenetic regulation of NLRP12 expression in SLE patients was also analyzed.

Results: We found that NLRP12 expression was significantly lower in PBMC isolated from SLE patients compared to healthy donors. The inverse correlation was observed in NLRP12 and IFNA gene expression as well as NLRP12 expression and amount of double-stranded DNA autoantibody in SLE patients. Interestingly, NLRP12 expression was gradually restored to the normal level after treatments in the patients. Results from ChIp and EMSA analysis indicated potential transcription factors (TFs) regulating NLRP12 promoter activity, thus lead to transcriptional suppression of NLRP12 in SLE PBMC.

Conclusion: In this study, expression level of NLRP12 has been demonstrated to be a biomarker of disease activity in SLE patients. Mechanistically, a specific transcription factor regulating NLRP12 expression in SLE PBMC is in accord with the same TF that suppresses NLRP12 expression in type I IFN treated-monocyte. This finding may offer clues and an explanation for SLE patients with type I IFN signature.

« Back to 2019 ACR/ARP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/nlrp12-regulates-interferon-%ce%b1-expression-and-is-a-biomarker-for-disease-activity-of-systemic-lupus-erythematosus/