Ameliorated course of glucose-6-phosphate isomerase (G6PI)-induced arthritis in IFN-gamma receptor knockout mice exposes an arthritis-promoting role of IFN-gamma

作者：Frey Oliver; Mitera Tania; Kelchtermans Hilde; Schurgers Evelien; Kamradt Thomas; Matthys Patrick^*

来源：Journal of Autoimmunity, 2011, 36(2): 161-169.

DOI：10.1016/j.jaut.2010.12.006

• Animal model
• T helper cells
• Osteoclastogenesis
• Interferon
• Adjuvant

The absence of IFN-gamma signaling leads to an increased inflammatory response in many murine models of autoimmune diseases induced by a CFA-assisted immunization schedule. We investigated the role of endogenous IFN-gamma in arthritis induced by immunization with glucose-6-phosphate isomerase (G6PI) in CFA in DBA/1 mice. Surprisingly, and in contrast to our previous findings in collagen-induced arthritis (CIA), G6PI-induced arthritis was found to be reduced in IFN-gamma receptor-deficient (IFN-gamma R KO) mice, demonstrating a proinflammatory role for IFN-gamma in this model. Milder disease in IFN-gamma R KO mice was associated with less vigorous innate and adaptive immune responses early (day 9) after immunization: less proliferation of myeloid cells in the spleen, less osteoclast formation, less G6PI-reactive Th cells (as measured by ex vivo stimulation and flow cytometry and by in vivo skin reactivity to G6PI) and lower G6PI-specific immunoglobulin serum levels. Surprisingly, on day 21, despite continued milder disease in IFN-gamma R KO mice, their Th cell responses were no longer diminished but augmented as compared to wildtype mice, and their numbers of immature myeloid splenocytes were also more increased.
These data reveal that IFN-gamma signaling is critical for the induction of the early immune responses which trigger G6PI-induced arthritis. The strikingly different clinical consequences of absent IFN-gamma signaling in G6PI-induced arthritis compared with the very similarly induced CIA emphasize that the role of a single cytokine in experimentally induced arthritis depends critically on the very nature of the inciting (auto) antigen and in particular on the kinetics of the disease manifestation elicited by the antigen.

• 出版日期2011-3