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

Mol Cell Endocrinol. 2017 Aug 15:451:88-96. doi: 10.1016/j.mce.2017.01.035. Epub 2017 Jan 25.

Abstract

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.

Keywords: Autoimmunity; GVHD; Immunosuppression; JAK; Myeloproliferative neoplasia; STAT.

Publication types

  • Review

MeSH terms

  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / pathology
  • Cell Movement
  • Cytokines / genetics
  • Cytokines / immunology
  • Gene Expression Regulation
  • Graft vs Host Disease / genetics
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / pathology
  • Graft vs Host Disease / prevention & control*
  • Humans
  • Immunologic Deficiency Syndromes / genetics*
  • Immunologic Deficiency Syndromes / immunology
  • Immunologic Deficiency Syndromes / pathology
  • Immunosuppressive Agents / therapeutic use*
  • Janus Kinases / antagonists & inhibitors*
  • Janus Kinases / genetics
  • Janus Kinases / immunology
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neoplasms / prevention & control*
  • Organ Transplantation
  • Protein Kinase Inhibitors / therapeutic use*
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / immunology
  • Signal Transduction

Substances

  • Cytokines
  • Immunosuppressive Agents
  • Protein Kinase Inhibitors
  • STAT Transcription Factors
  • Janus Kinases