Finally, we also investigated IL1RL1 coding region variation and established that cells carrying the IL1RL1 TIR domain asthma risk haplotype (Signal D) presented with an exaggerated inflammatory response to IL-33 that is more amenable to the antiinflammatory effects of either anti–IL-33 or anti-IL1RL1 monoclonal antibodies. Here, IL1RL1 is linked to asthma.