CORDIS
EU research results

CORDIS

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regulation of B-cell Epitope migration and Autoimmunity by T follicular helper cells

Project information

Grant agreement ID: 796988

Status

Ongoing project

  • Start date

    1 July 2018

  • End date

    30 June 2021

Funded under:

H2020-EU.1.3.2.

  • Overall budget:

    € 260 929,80

  • EU contribution

    € 260 929,80

Coordinated by:

UNIVERSITAIR MEDISCH CENTRUM UTRECHT

Netherlands

Objective

The detection of autoantibodies typically appear a few years prior to clinical autoimmune disease and their reactivity can drift at or after disease onset. The laboratory of M.C. Carroll (outgoing institute) has developed a murine model (ARTEMIS; Autoreactive B-cell driven T-dependent Epitope Migration towards Immunity to Self) where the presence of a single autoreactive B cell clone drives activation, expansion and differentiation of other autoreactive B-cells in spontaneous germinal centers (GC) followed by autoantibody deposition in the kidney. These autoreactive B-cells target multiple other self-antigens (also known as epitope spreading) and are independent of the initial trigger once tolerance is broken. Follicular T helper (Tfh) cells play a prominent role in the selection of B-cells in the GC and have been linked to excessive GC formation, high-level production of pathogenic autoantibodies and end-organ damage in murine and human autoimmune disease. With this project I will address the role of Tfh cells in the maturation process of the self-reactive B-cell response and epitope spreading as observed in human autoimmune disease. Preliminary results show dependence of T cells, the extent and nature of T-cell involvement is however not yet addressed. I will utilize the mixed bone-marrow chimera model (ARTEMIS) in combination with selected strains altered in important factors for Tfh function and differentiation. As the GC reaction is a highly dynamic process we will visualize this utilizing multi-photon intravital microscopy and analyze important interactions of Tfh cells in the developing autoreactive GC. The development of autoreactivity from WT B-cells in the ARTEMIS model better reflects natural autoreactive GC behavior and human autoimmune disease and could therefore favor the transition of potential therapeutic targets from murine to human disease.
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Coordinator

UNIVERSITAIR MEDISCH CENTRUM UTRECHT

Address

Heidelberglaan 100
3584 Cx Utrecht

Netherlands

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 260 929,80

Partners (1)

CHILDREN'S HOSPITAL CORPORATION

United States

Project information

Grant agreement ID: 796988

Status

Ongoing project

  • Start date

    1 July 2018

  • End date

    30 June 2021

Funded under:

H2020-EU.1.3.2.

  • Overall budget:

    € 260 929,80

  • EU contribution

    € 260 929,80

Coordinated by:

UNIVERSITAIR MEDISCH CENTRUM UTRECHT

Netherlands