AHR and Arthritis: Our studies with this cusp ligand have also provided a mechanistic basis for the long-observed association between RA, cigarette smoking and carriage of SE-coding alleles (117), by demonstrating that in the presence of aryl hydrocarbon receptor (AhR) agonists - environmental pollutants found in cigarette smoke - the activation potency of the SE-mediated pathway is amplified synergistically with resultant augmented inflammatory response and bone erosive damage that lead to more severe experimental arthritis in mice (21).