Background/Purpose:  Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are cytoplasmic sensors that response to danger signals released by invading pathogen or self-damaged tissues. NLRP12 is a member of the NLR protein family and classified as a negative regulator of inflammation and autoimmune response. However, the role of NLRP12 for autoimmune arthritis has not been explored. To investigate the NLRP12 effect on rheumatoid arthritis (RA), we decided to study whether NLRP12 deficiency would have an impact on disease outcome using the RA model of collagen-induced arthritis (CIA).

Methods:  C57BL/6 Nlrp12^-/-mice were obtained from Dr. Jenny Ting’s laboratory and backcrossed onto DBA/1J background for eleven generations. These mice and wild type (WT) mice were induced with CIA. Arthritis development was monitored for 45 days, and joint samples were harvested for histological analysis and RT-PCR detection of cytokine production in the joints.

Results:  We found that Nlrp12^-/- mice show reduced clinical scores and diminished paw swelling compared to WT mice throughout disease development. Histological joint sections of Nlrp12^-/- mice show a decrease in immune cell infiltration to the synovial membrane and space, reduced cartilage damage, and less bone erosion. Then we examined the cytokine expression in the joints of Nlrp12^-/- mice and found that the proinflammatory cytokines IL-1beta and IL-6 were substantially reduced compared to WT mice, whereas TNFalpha and IL-17 expressions remain similar between Nlrp12^-/- mice and WT mice.

Conclusion:  Our results indicate that NLRP12 deficiency reduces autoimmune arthritis in the CIA model by decreased inflammation and proinflammatory cytokines in the joints. Further studies are needed to identify the innate immune cells and the molecular pathways in which NLRP12 functions in autoimmune arthritis as they could lead to potential therapeutic targets for patients with RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/role-of-nlrp12-on-disease-severity-in-autoimmune-arthritis/