The role of the transcription factors Hobit and Blimp-1 on TNF-dependent arthritis in mice 2412

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Abstract Description Background Although chronic autoinflammatory arthritis is widely distributed throughout the world, its exact etiology and pathogenesis is still poorly understood. A deeper insight into the underlying disease mechanisms could lead to better treatments for patients. Objectives To investigate the influence of the transcription factors Blimp-1 and Hobit on experimental arthritis Methods We crossed TNFΔARE mice spontaneously developing arthritis to Hobit-/-Blimpflox/flox Lck-Cre mice and studied the arthritis phenotype depending on Hobit- and/or Blimp-deficiency. Accordingly, clinical parameters were analyzed up to week 14. Cell infiltration and osteoclast activity was evaluated histologically. Moreover, mononuclear cells were isolated from blood and inflamed joints and profiled by flow cytometry and transcriptomics. Results Hobit-/-Blimpflox/flox Lck Cre+ TNFΔARE and Hobit+/+ Blimpflox/flox Lck-Cre+ TNFΔARE mice had improved overall disease activity compared to wildtype TNFΔARE mice. In particular, clinical arthritis activity was reduced accompanied by reduced osteoclast numbers. We observed no difference in the abundance of immune cell infiltration to the inflamed joints, but flow cytometry revealed qualitative differences in T cells. Moreover, we observed a significant influence of Blimp-1 on IL-22 expression. Conclusion Our data indicate a potential influence of Blimp-1 on IL-22 expressing cells and their potential involvement in the pathogenesis of TNF-dependent arthritis in mice. Topic Categories Cellular Adhesion, Migration, and Inflammation (CAM)

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