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GITR+ regulatory T cells in the treatment of autoimmune diseases

Maria Grazia Petrillo1, Simona Ronchetti1, Erika Ricci1

  • 1Department of Medicine, Section of Pharmacology, University of Perugia, Italy.

Autoimmunity Reviews
|December 3, 2014
PubMed

Insights

New therapies targeting regulatory T cells (Tregs) show promise for autoimmune diseases. Glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) plays a key role in Treg expansion for potential curative treatments.

Area of Science:

  • Immunology
  • Autoimmune Diseases
  • Cellular Therapy

Background:

  • Autoimmune diseases significantly impact life expectancy and quality of life.
  • Current treatments for autoimmune diseases have adverse effects and are not curative, necessitating lifelong immunosuppression.
  • There is an urgent need for safe and effective curative therapies for autoimmune diseases.

Purpose of the Study:

  • To review the role of glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) in regulatory T cell (Treg) differentiation and expansion.
  • To explore novel therapeutic strategies for autoimmune diseases based on GITR-targeted Treg expansion.
  • To discuss the potential of in vivo and in vitro Treg expansion for treating autoimmune conditions.

Main Methods:

  • Review of murine and human studies on GITR's role in Treg biology.
  • Analysis of CD4(+)GITR(+) peripheral Tregs (pTregs) in patients with Sjögren syndrome and systemic lupus erythematosus.
  • Evaluation of GITR as a cell surface marker for Treg identification.

Main Results:

  • Glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) is crucial for both thymic Treg (tTreg) and peripheral Treg (pTreg) expansion.
  • Expanded CD4(+)GITR(+) pTregs are associated with milder forms of Sjögren syndrome and systemic lupus erythematosus.
  • GITR demonstrates superiority over other markers for differentiating Tregs from other CD4(+) T cells.

Conclusions:

  • Targeting GITR for in vivo Treg expansion using GITR-triggering drugs is a potential therapeutic approach.
  • In vitro expansion of GITR(+) Tregs for infusion offers another promising cellular therapy strategy.
  • Further research into the advantages, technical challenges, and safety of GITR-targeted Treg therapies is warranted.

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