TREG

Analysis of regulatory T cell proliferation and apoptosis in vivo at the cellular and molecular level

 Partecipanti

Mappa

 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

 Obiettivo del progetto (Objective)

'Foxp3 regulatory T cells are critical for controlling the degree of immune activation during infection, autoimmunity and allergy. Despite the importance of this cell lineage to human health, relatively little is known about the molecular and cellular control of their differentiation and homeostasis. In order to rectify this deficit we propose to investigate the properties of proliferation and apoptosis during expansion, contraction and homeostatic stages, using sophisticated genetic models. We will also investigate the role of Bcl-2 family member genes and the IL2 / Pdl1 axis in the molecular control over these cellular properties. By dissecting the factors controlling regulatory T cell numbers we ultimately seek routes to make this process amenable to therapeutic manipulation.'

Introduzione (Teaser)

While regulatory T cells play an important role in the immune system, little is known about their differentiation and homeostasis. An EU-funded project is filling the gap through in vivo studies.

Descrizione progetto (Article)

Regulatory T cells prevent excessive immune reactions. In autoimmune disease, regulatory T cell deficiency can allow the immune system to attack the body's own tissues. In cancer, excessive activity of regulatory T cells prevents the immune system from destroying cancer cells.

Foxp3+ (forkhead box P3) T cells are regulatory cells that are critical for controlling the degree of immune activation during infection, autoimmunity and allergy. These cells are important for self / non-self- discrimination. The EU-funded TREG (Analysis of regulatory T cell proliferation and apoptosis in vivo at the cellular and molecular level) project was dedicated to elucidating mechanisms regulating Foxp3+ T cells.

TREG used genetic models to study proliferation and apoptosis during expansion, contraction and homeostatic stages. Scientists identified Mcl-1 (induced myeloid leukemia cell differentiation protein) as a primary factor for regulatory T cell homeostasis, making it a potential drug target. Interleukin 2 (IL-2) affected both Mcl1 and T cell survival.

Experiments revealed that the apoptotic proteins Bax, Bak and Bim are the key regulators of circulating Foxp3+ T cells. Interestingly, Bcl-2 (B-cell lymphoma 2) proteins hardly played any role in controlling regulatory T cell homeostasis. TREG analysed the kinetics of regulatory T cell response in connection with disturbed homeostasis. Project outcomes resulted in two patent applications.

Understanding the factors controlling regulatory T cell numbers is the first step to make this process amenable to therapeutic manipulation. The results will have important implications for patients suffering from autoimmune disease.