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

Project description

Novel targets to improve allogeneic hematopoietic stem cell transplantation

B cells are pivotal in chronic graft-versus-host disease (cGVHD), which is the most common cause of late non-relapse morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Recent single-cell RNA-sequencing studies demonstrated that AIM2 (absent in melanoma 2) is upregulated in cGVHD patient B cells. Upon DNA binding, the AIM2 protein induces AIM2 inflammasome formation and triggers pro-inflammatory cytokine secretion. Other related studies showed that the enzyme DNase1L3 regulating extracellular DNA exposure could play a pivotal role in B cell development. The EU-funded DABAT project will investigate AIM2 and DNase1L3 in human B cells and in mouse in vivo models. The research will address intrinsic molecular programmes underpinning B cell pathobiology and agents targeting B cells which can be developed for cGVHD treatment.

Coordinator

UNIVERSITE DE BORDEAUX
Net EU contribution
€ 275 619,84
Address
Place Pey Berland 35
33000 Bordeaux
France

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Region
Nouvelle-Aquitaine Aquitaine Gironde
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00

Partners (1)

Partner

Partner organisations contribute to the implementation of the action, but do not sign the Grant Agreement.

DUKE UNIVERSITY
United States
Net EU contribution
€ 0,00
Address
Allen Building 207
27708 Durham Nc

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Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 177 265,92