Role of JAK inhibitors and immune cells in transplantation

Cytokine Growth Factor Rev. 2019 Jun:47:62-73. doi: 10.1016/j.cytogfr.2019.05.002. Epub 2019 May 11.

Abstract

Immunosuppressive challenge after transplantation has dual objectives, namely, to efficiently inhibit immune populations involved in acute, chronic, humoral or cellular transplant rejection while minimizing the effect on immune integrity toward pathogens. The current immunosuppressive strategies show limited efficacy and remain associated with strong side effects, and thus, it is essential to develop new strategies. The use of Janus kinase (JAK) inhibitors is one of the new strategies focusing on cytokine pathways. Specifically, the first-generation JAK inhibitors (JAKis) showed low specificity toward the four known JAK molecules and did not exhibit better effects than calcineurin inhibitors, which constitute the standard treatment posttransplantation. However, because the new generation of JAKis present higher specificity, we are gaining further insights on the response of cells to these inhibitions. This review focuses on the impact of JAKis on different immune cell subsets, focusing on their role in transplantation.

Keywords: Cytokine; Immunosuppressive treatment; JAK; JAK inhibitor; Transplantation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Dendritic Cells / immunology*
  • Hematopoietic Stem Cells / immunology
  • Humans
  • Janus Kinase Inhibitors / pharmacology*
  • Janus Kinases / immunology
  • Leukocytes / immunology*
  • Macrophages / immunology*
  • Nitriles
  • Organ Transplantation*
  • Pyrazoles / pharmacology*
  • Pyrimidines
  • Signal Transduction

Substances

  • Janus Kinase Inhibitors
  • Nitriles
  • Pyrazoles
  • Pyrimidines
  • ruxolitinib
  • Janus Kinases