H2020Индивидуална стипендия2020–2023

DABAT · DNA-sensing by AIM2 in activated B cells: novel targets to improve allogeneic haematopoietic stem cell transplantation

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

Период: 2020-10-01 → 2023-09-30
Финансиране от ЕС: 275 620 €
Участници: 2
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Механизмите на B-клетките при трансплантация на стволови клетки се анализират, за да се разбере защо те произвеждат вредни антитела срещу тъканите на пациента. Това помага за разработването на нови терапии за подобряване на резултатите след лечението.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

DNA-sensing by AIM2 in activated B cells: novel targets to improve allogeneic haematopoietic stem cell transplantation

Allogeneic haematopoietic cell transplantation (allo-HCT) is the standard therapy for several haematological cancers and diseases, with more than 30,000 allo-HCTs carried out annually worldwide. In allo-HCT, the recipient receives a new immune system to correct an immune deficiency or to cure a leukaemia. Most of the allo-HCT are performed with a donor who presents genetic disparities with the recipient. These genetic disparities activate the new immune system which attacks recipient’s organs and tissues. This process is called chronic graft-vs-host disease (cGVHD). Among immune cells, T cells are required for cGVHD to occur. However, B cells also play a central role by producing pathogenic antibodies. The therapeutic strategies currently available for cGVHD are limited and need to be improved. Our overarching hypothesis is that, after allo-HCT, tolerance checkpoints in pathological B cells are dysregulated via B cell intrinsic mechanisms. Our overarching goal is to understand intrinsic B cell pathways that drive altered B cell homeostasis post-transplantation, so that we can develop new therapeutic strategies to improve transplantation outcomes.

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

Цел на проекта

A recent paradigm shift is that B cells are pivotal in chronic graft-versus-host-disease (cGVHD), which is the most relevant cause of late non-relapse morbidity and mortality after allogeneic haematopoietic stem cell transplantation. DABAT’s project hypothesis is that 1) DNA-sensing by AIM2 supports cGVHD pathological B cells through autocrine regulations and that 2) their DNase1L3 expression modulates DNA-sensing by AIM2. Doctor Sarantopoulos (Duke University, US, supervisor for the outgoing phase) recently performed a single cell RNA-Sequencing experiment showing that AIM2 is upregulated in cGVHD patient B cells. Upon DNA binding, the AIM2 protein induces AIM2 inflammasome formation that triggers pro-inflammatory cytokines secretion. The survival and function of pathological B cells in cGVHD seem to be based on similar mechanisms to those of marginal zone (MZ) B cells. Doctor Sisirak (Bordeaux University, France, supervisor for the incoming phase) showed that DNase1L3, a major enzyme regulating extracellular DNA exposure, could play a pivotal role in MZ B cells development. The researcher will conduct the DABAT project under the supervision of these two internationally recognized experts in cGVHD B cells and DNase1L3. He will study AIM2 and DNase1L3 in human B cells and in mouse models. This fellowship will provide him with advanced technical training in B cell studies, flow cytometry, transcriptomic, histopathology and animal handling. He could identify intrinsic molecular programs underpinning B cell pathobiology, so that agents targeting B cell can be developed to treat cGVHD. He will be the main spokesperson of the project to a large audience. This fellowship will be a crucial step to extend his knowledge, to develop his communication, management and leadership skills, and to enlarge his international professional network. He will then become a mature and independent researcher enriching EU expertise and networking in Immunology and Transplant Immunology.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITE DE BORDEAUX · BordeauxКоординаторФранция
DUKE UNIVERSITY · Durham NcСъединени щати