Targeting Metabolism as a Platform for Inducing Allograft Tolerance in the Absence of Long-Term Immunosuppression

Front Immunol. 2020 Apr 9:11:572. doi: 10.3389/fimmu.2020.00572. eCollection 2020.

Abstract

Transplant tolerance in the absence of long-term immunosuppression has been an elusive goal for solid organ transplantation. Recently, it has become clear that metabolic reprogramming plays a critical role in promoting T cell activation, differentiation, and function. Targeting metabolism can preferentially inhibit T cell effector generation while simultaneously promoting the generation of T regulatory cells. We hypothesized that costimulatory blockade with CTLA4Ig in combination with targeting T cell metabolism might provide a novel platform to promote the induction of transplant tolerance.

Keywords: costimulation blockade; immunology; metabolism; model; mouse; rejection; transplantation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Abatacept / pharmacology*
  • Allografts
  • Animals
  • Deoxyglucose / pharmacology*
  • Diazooxonorleucine / pharmacology*
  • Glycolysis / drug effects
  • Immunosuppression Therapy / methods*
  • Immunosuppressive Agents / pharmacology
  • Lymphocyte Activation / drug effects
  • Metformin / pharmacology*
  • Mice
  • T-Lymphocytes / drug effects
  • Transplantation Tolerance / drug effects*

Substances

  • Immunosuppressive Agents
  • Diazooxonorleucine
  • Abatacept
  • Metformin
  • Deoxyglucose