Background NLRP12 (NOD-like receptor family (NLR) pyrin domain containing 12) is an innate immune check-point in regulating type I IFNs expression. Since NLRP12 may participate in the pathogenesis of lupus, its role in lupus nephritis remained unknown.
Methods Wild type C57BL/6 and Nlrp12-/- mice in 12-week-old age were injected intra-peritoneally with a single dose of 500μl of pristane (2,6,10,14-tetramethylpentadecane, TMPD), and mice were sacrificed from 1st to 9th months after injection. Serum were collected for evaluation autoantibodies and renal functions. Kidneys sections were collected for immunoglobulin (IgG) evaluation and periodic-acid-Schiff (PAS) staining. Lupus prone mice with C57BL/6-Faslpr and C57BL/6- Faslpr-Nlrp12-/- mice were harvested and collected from 7th to 11th months.
Results Among animal models, both pristane induced mice and Faslpr mice revealed increasing autoantibodies production and severity of glomerulonephritis in Nlrp12-/- group in comparison with Nlrp12+/+ ones. Immunofluorescence staining for IgG revealed more profound deposition from 1st to 9th months after pristane injection group, with renal glomerulus damage from PAS staining. For Faslpr-Nlrp12-/- mice, more IgG deposition was noted. The CD43 staining revealed similar trend of both animal models. In serological evaluation, the dsDNA antibody in both animal model revealed significantly increased titer in Nlrp12-/- deficient ones (both group P < 0.01). Proteinuria analysis and serum creatinine all showed worsened presentation in Nlrp12-/- deficient mice.
Conclusions Animal models revealed Nlrp12 deficiency could exacerbate the lupus disease severity and progression of lupus nephritis in 2 different mouse models, both in histologic examinations and serological changes, reflecting the importance of Nlrp12 in controlling lupus pathogenesis.
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