H2020Индивидуална стипендия2017–2019

DISTRICT · DECIPHERING THE ROLE OF TRIB1 IN REGULATORY T CELLS

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2017-07-01 → 2019-06-30
Финансиране от ЕС: 185 076 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Протеинът TRIB1 и неговата роля в регулаторните Т-клетки се анализират, като се проучва връзката му с гена FOXP3. Това помага за по-доброто разбиране на имунни заболявания, рак и процесите при трансплантация на бъбрек.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

DECIPHERING THE ROLE OF TRIB1 IN REGULATORY T CELLS

The immune system homeostasis relies on regulatory T cells (Tregs) which are indispensable for peripheral tolerance, notably by preventing the expansion of autoreactive T cells and adjusting the balance between pro and anti-inflammatory signals. Thereby, Tregs are involved in widespread immune-related diseases including autoimmune ones like type-1 or type-2 diabetes and rheumatoid arthritis, and cancers. Additionally, it is known that Tregs play an important role in long-term graft survival in different experimental models and in human kidney transplantation. Tribbles pseudokinase 1 (TRIB1) is a serine-threonine kinase-like protein with no known catalytic activity which has been described in different pathological settings including cancer or chronic inflammatory diseases such as atherosclerosis and organ transplantation. Previous studies by our group demonstrated the potent value of TRIB1 as a biological marker for chronic antibody-mediated rejection in kidney transplant recipients. TRIB1 participates to various biological functions and is expressed by a large variety of cells suggesting that its function would be environment and tissue dependent. One particularly interesting finding is the over-expression of TRIB1 in Tregs and the high correlation of TRIB1 gene expression with FOXP3 gene and protein expressions suggesting both molecules are co-regulated in Tregs which need further investigation. TRIB1 lack of catalytic domain suggests TRIB1 acts as a scaffold protein, but the role of Trib1 in Tregs remains to be elucidated. The overall purpose of DISTRICT was to investigate the role of TRIB1 in the Treg biology. The results from this project are the first to highlight the role of TRIB1 in Treg and have implications in immune-related pathologies.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

The role of regulatory T cells (Tregs) is crucial to maintain immune homeostasis by controlling peripheral tolerance. A better understanding in the molecular mechanisms involved in the biology of these Treg cells could improve their expansion and selection to treat immune-related diseases, achieve immunosuppression-free organ transplantation and to specifically target them in cancer. We reported on the over-expression of Tribbles-1 (TRIB1) in Tregs compared to their counterpart naïve T cells and that TRIB1 interacts with the master molecule of Tregs, FOXP3, a transcription factor essential for Treg suppressive activity. These results suggest still non explored potential links between TRIB1 in Tregs biology. Our goal is thus to decipher the role of TRIB1 in the Treg homeostasis and functions, through 3 main axes: 1) deciphering the function of TRIB1 in Tregs in vitro, 2) highlighting its implication in vivo using a combinaison of immune-related models and 3) discovering the signalling pathway of TRIB1 in Tregs. These results would not only increase TRIB1 mechanistic knowledge but also increase comprehension of Treg biology and bring opportunities to identify new strategies to modulate Tregs for immunotherapy.

Оригинален текст от CORDIS (на английски).

Участници

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE · ParisКоординаторФранция