The present invention is directed to compositions and methods to treat an autoimmune disease in a subject, comprising an insulin-like 6 (Insl6) agent, such as an Insl6 polypeptide or variant or fragment thereof, or a nucleic acid encoding Insl6 poly peptide or variant or fragment thereof. Aspects of the present invention relate to use of Insl6 agents to reduce T-regulatory (Treg) cells in the subject and to reduce pro-inflammatory cytokines in a subject with an autoimmune disease such as a muscle autoimmune disease. The present invention also relates to methods and kits for the treatment of autoimmune diseases in a subject, and methods to diagnose a subject with an autoimmune disease such as myositis.