JAK/STAT disruption induces immuno-deficiency: Rationale for the development of JAK inhibitors as immunosuppressive drugs.

Cytokines are mediating immune cells responses through the activation of the JAK/STAT signaling pathway. Being critical for immune cells, a defective JAK/STAT signaling leads to various immune disorders, such as immunodeficiency. In contrast, hyperactivation of JAK/STAT signaling is linked to autoimmunity and cancer. Targeting the JAK/STAT proteins by small protein inhibitors impedes immune cell function by uncoupling cells from cytokine effects and by interfering with functional immune cell hallmarks, such as cell migration. This review will explore immune syndromes driven by JAK/STAT deregulation and discuss the emerging role of JAK inhibitors as immunosuppressive drugs used in autoimmunity and transplantation medicine.