IL-10 is a non-redundant inflammatory modulator that suppresses arthritis development in Borrelia burgdorferi infected mice. Infected B6 IL-10−/− mice were previously found to have a prolonged interferon-inducible response in joint tissue. Infection of B6 IL-10 reporter mice identified macrophages and CD4+ T cells as the primary sources of IL-10 in the infected joint tissue, suggesting that early local production of IL-10 dampened the pro-arthritic interferon response. Treatment of B6 IL-10−/− mice with anti-IFN-γ reduced the increase in arthritis severity and suppressed interferon-inducible transcripts to wild type levels, thereby linking dysregulation of IFN-γ to disease in the B6 IL-10−/− mouse. Arthritis in B6 IL-10−/− mice was associated with elevated numbers of NK cell, NKT cell, α/β T cell, and macrophage infiltration of the infected joint. FACS lineage sorting revealed NK cells and CD4+ T cells as sources of IFN-γ in the joint tissue of B6 IL-10−/− mice. These findings suggest the presence of a positive feedback loop in the joint tissue of infected B6 IL-10−/− mice, where production of inflammatory chemokines, infiltration of IFN-γ producing cells, and additional production of inflammatory cytokines result in arthritis. This mechanism of arthritis is in contrast to that seen in C3H mice, where arthritis development is linked to transient production of Type I interferon, and develops independently of IFN-γ. Due to the sustained interferon response driven by NK cells and T cells, we propose the B6 IL-10−/− mouse as a potential model to study the persistent arthritis observed in some human Lyme disease patients.
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