Tolerogenic dendritic cells can inhibit pyroptosis of spleen cells in collagen-induced arthritis rats

doi:10.12307/2023.498

Abstract

Abstract: BACKGROUND: In our previous study, we successfully constructed antigen-specific tolerogenic dendritic cells using nuclear factor-kappa B oligodeoxynucleotide decoy, and used them to effectively intervene a collagen-induced arthritis rat model. However, the therapeutic mechanism remains to be further studied.
OBJECTIVE: To investigate the effect of tolerogenic dendritic cells on pyroptosis of spleen cells in collagen-induced arthritis rats.
METHODS: Bone marrow-derived dendritic cells were extracted and used to construct tolerogenic dendritic cells using nuclear factor-kappa B oligodeoxynucleotide decoy. Nine Sprague-Dawley rats were randomly divided into control group, model group, and treatment group, with three rats in each group. The latter two groups were used to establish rheumatoid arthritis models. Initial immunization was subcutaneous injection of bovine type II collagen emulsion on the left foot plantar; booster immunization was multiple injections of bovine type II collagen emulsion at the base of the tail on the 14th day after the initial immunization. Rats in the model and treatment groups were given normal saline and tolerogenic dendritic cells into the tail vein, respectively, on the 20th day after the initial immunization. Relevant measurements were performed on the 35th day after the initial immunization.
RESULTS AND CONCLUSION: (1) Compared with the model group, arthritis index score in the treatment group decreased significantly (P < 0.05). (2) Gross and pathological observations showed the ankle joints of the rats were severely swollen in the model group and slightly swollen in the treatment group. Hematoxylin-eosin staining results showed that compared with the control group, the synovium of the ankle joint had obvious hyperplasia, accompanied by inflammatory cell infiltration and bone erosion; compared with the model group, the treatment group had reduced synovial hyperplasia, bone erosion and inflammatory cell infiltration of the ankle joint. (3) Serum interleukin 1β level was higher in the model group than the control group (P < 0.01) and lower in the treatment group than the model group (P < 0.01). (4) Western blot results showed that compared with the control group, the protein expressions of NLR family pyrin domain containing 3, pro-caspase-1, caspase-1, GSDMD-NT, pro-interleukin 1β, and interleukin 1β in the spleen were significantly increased in the model group (P < 0.05). Compared with the model group, the protein expressions of spleen NLR family pyrin domain containing 3, pro-caspase-1, caspase-1, GSDMD-NT, pro-interleukin 1β, and interleukin 1β were all decreased in the treatment group (P < 0.05). (5) In conclusion, tolerogenic dendritic cells may alleviate inflammatory responses in collagen-induced arthritis rats by inhibiting the pyroptosis of spleen cells and the expression of interleukin-1β.

Key words: tolerogenic dendritic cell, collagen-induced arthritis, NLRP3, interleukin 1β, pyroptosis, rheumatoid arthritis

CLC Number:

Long Tiaoyu, Bao Lunmin, Wan Xiufang, Li Honghong, Zhang Yundong, Jiang Hongmei. Tolerogenic dendritic cells can inhibit pyroptosis of spleen cells in collagen-induced arthritis rats[J]. Chinese Journal of Tissue Engineering Research, 2023, 27(33): 5363-5369.

Figures/Tables 6

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