Establishment and evaluation of collagen antibody-induced arthritis model in PD-L2 knockout mice

Objective To establish a collagen antibody-induced arthritis (CAIA) model of PD-L2 knockout mice and to evaluate the immune status of mice.Methods A CAIA model of wild-type (WT) and programmed cell death ligand 2 (PD-L2) gene knockout (PD-L2-/-) was established. Mouse body weight and hindpaw thickness are measured and joint scores are performed. Hematoxycin-eosin (HE), masson and modified saffron-O and fast green (safranin O) staining were used to evaluate the inflammation of mouse joint tissues. Flow cytometry was used to detect the proportions of T cells, B cells, natural killer (NK) cells and monocytes in the spleen of the two groups, and the inflammatory factors interferon-γ(IFN-γ), interleukin-4 (IL-4) and IL-17 secreted by CD4+ T cells, CD11b+ cells and NK cells were detected by permeabilization flow cytometry.Results The CAIA models of mice in both WT group and PD-L2-/- group were successfully established. After modeling, the body weight of the WT -CAIA group and the PD-L2-/--CAIA group decreased, the thickness of the hind paws increased, and the joint score increased. The joint swelling score, synovial thickening score, inflammatory cell infiltration score and cartilage erosion score in the PD-L2-/--CAIA group were lower than those in the WT-CAIA group, but there was no significant difference (P>0.05). The proportions of CD4+ T cells, CD8+ T cells, CD8+ central memory T cells and NK cells in the PD-L2-/--CAIA group were lower than those in the WT-CAIA group (P<0.05). The secretion of IFN-γ and IL-17 by CD4+ T cells in the PD-L2-/--CAIA group was lower than that in the WT-CAIA group (P<0.05), the secretion of IFN-γ, IL-4 and IL-17 by CD11b+ cells in the PD-L2-/--CAIA group was lower than that in the WT-CAIA group (P<0.05), and the secretion of IFN-γ and IL-17 by NK cells in the PD-L2-/--CAIA group was lower than that in the WT-CAIA group (P<0.05)。Conclusion PD-L2 knockout mice can still induce the onset of arthritis, but the degree of inflammation of joint tissue is lower than that of WT group.