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Chronic immune inflammation results from a failure to resolve persistent inflammatory stimuli. The resolution of inflammation is critically dependent on the carefully balanced orchestration of immune responses. “Inhibitory” KIR immune receptor interactions with HLA-class I have been implicated in diverse chronic inflammatory disorders including spondyloarthritis, Crohn’s disease and Pemphigus vulgaris. I will discuss how “inhibitory” KIR immune receptor interactions could promote inflammation using knowledge gained from our studies on HLA-B27 binding to immune receptors.