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Tissue repair functions of MAIT cells: integrating thymic pre-commitment and peripheral signals

Project information

Grant agreement ID: 885435

Status

Grant agreement signed

  • Start date

    1 October 2020

  • End date

    30 September 2025

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 2 499 500

  • EU contribution

    € 2 499 500

Hosted by:

INSTITUT CURIE

France

Objective

Mucosal associated invariant T cells (MAITs) represent an abundant subset in humans with unique specificity for microbial metabolites. MAIT conservation along evolution indicates important, non-redundant functions. Despite changes in MAIT frequency and phenotype in several infectious and non-infectious diseases, their functions are still unclear. By contrast with mainstream CD4+ or CD8+ T cells, MAITs differentiate into effector cells during thymic development. How the differentiation program imparted in the thymus is modified by tissue and environmental cues to determine MAIT functions in tissues is not known. Our preliminary data support a new function for MAITs in boosting tissue repair in skin wound healing and flu infection. Thus, MAITs would either repair tissues or inflict tissue damage when fighting microbes according to the stage of the disease. To understand how and when the different MAIT functions are turned on and off in vivo we will study: 1) How is the thymic MAIT differentiation program modulated by tissue and environmental cues to determine the location and effector functions of MAITs in skin and lung at steady state? To this end we will develop new genetic methods to modify MAIT development or functions. 2) What are the effector functions of MAITs leading to protection during skin wound healing and flu infection? We will determine the cell types MAITs affect and identify the mediators secreted by MAIT cells. 3) What triggers MAIT protective effect? We will identify the drivers of MAIT activation and assess the requirement for cognate or non-cognate (cytokines) interactions. Wound healing of human skin explants will test the therapeutic potential of modulating MAIT activation. Our results will provide unique insight on the functions of MAIT cells with important implications for therapy of diseases in which MAIT triggering (or inhibition) could be beneficial (or deleterious) such as wounds or infections that damage tissues and thus require repair.

Host institution

INSTITUT CURIE

Address

Rue D'Ulm 26
75231 Paris

France

Activity type

Research Organisations

EU Contribution

€ 2 499 500

Beneficiaries (1)

INSTITUT CURIE

France

EU Contribution

€ 2 499 500

Project information

Grant agreement ID: 885435

Status

Grant agreement signed

  • Start date

    1 October 2020

  • End date

    30 September 2025

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 2 499 500

  • EU contribution

    € 2 499 500

Hosted by:

INSTITUT CURIE

France