Specifically, in the spontaneous IL-1rn−/− mouse model of autoimmune arthritis, TLR4 signaling by the microbiome appears to be responsible for the induction of arthritis, as germ-free IL1rn−/− mice or conventional IL-1rn−/− TLR4−/− mice are protected from autoimmune arthritis [19]. Here, IL1RN is linked to arthritic joint disease.