Autoimmunity could be initiated in lung and perpetuated in muscle. Epidemiologic studies suggest cigarette smoking as a key environmental risk factor. Smoking, or other irritants, could initiate Jo-1 cleavage or modification. Granzyme B-cleaved Jo-1 will attract mononuclear cells, which can process and present the Jo-1 autoantigen to the immune system. Similarly, Jo-1 is overexpressed in affected muscle and hence a similar pathway as described for the lung could also perpetuate adaptive immune reactions in the muscle. DC, dendritic cell; NK, natural killer; Th1, T helper 1.