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Epi-Tinn
FunderFrench National Research Agency (ANR)
Funder Contribution €636,917.00
DurationFrom 01 Jan 2026
Project codeANR-25-CE15-5339
Open Access mandatePublications: NoResearch data: No
Identifiers
Description
Innate abT cells are a subset of T lymphocytes that acquire effector functions directly during thymic development, independently of pathogen exposure. They play crucial roles in tissue repair and immune responses against bacteria, viruses and tumours owing to their abundance, their positioning in non-lymphoid tissues, rapid responses to stimulation, and versatile effector functions. These unique features are programmed during thymic differentiation by the master transcription factor promyelocytic leukemia zinc-finger protein (PLZF, encoded by the ZBTB16 gene) but the mechanisms of action and the role of PLZF in innate T cell functions in peripheral tissues remain poorly understood, primarily because the appropriate tools and technologies were lacking. Our project aims to discover direct targets and co-regulators of PLZF in two major innate T cell populations (MAIT and iNKT cells), both during thymic development and in peripheral tissues, using cutting-edge molecular approaches and an innovative mouse model with inducible PLZF deletion. Mouse and human innate T cells will be studied in parallel to ensure translational relevance to our findings. Additionally, we will determine the role of PLZF in controlling MAIT and iNKT cells ability to reside in non-lymphoid tissues and to respond swiftly to stimulation. How PLZF ultimately governs innate T cell functions will be determined using two disease models to probe the tissue-repair and anti-microbial functions of innate T cells in vivo. Altogether, this proposal brings together complementary expertise in innate T cell biology and in epigenetics to elucidate the mechanisms by which PLZF, a key transcriptional regulator, influences the development and function of major immune cell populations, both in mice and humans. Our innovative approaches may reveal the epigenetic regulation of innate T cells with unprecedented depth and resolution. Since PLZF is involved in the development of innate lymphoid cells and a subset of gdT cells, the Epi-Tinn project may identify new targets for the specific modulation of an array of immune cells with clinical relevance in humans.
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Innate abT cells are a subset of T lymphocytes that acquire effector functions directly during thymic development, independently of pathogen exposure. They play crucial roles in tissue repair and immune responses against bacteria, viruses and tumours owing to their abundance, their positioning in non-lymphoid tissues, rapid responses to stimulation, and versatile effector functions. These unique features are programmed during thymic differentiation by the master transcription factor promyelocytic leukemia zinc-finger protein (PLZF, encoded by the ZBTB16 gene) but the mechanisms of action and the role of PLZF in innate T cell functions in peripheral tissues remain poorly understood, primarily because the appropriate tools and technologies were lacking. Our project aims to discover direct targets and co-regulators of PLZF in two major innate T cell populations (MAIT and iNKT cells), both during thymic development and in peripheral tissues, using cutting-edge molecular approaches and an innovative mouse model with inducible PLZF deletion. Mouse and human innate T cells will be studied in parallel to ensure translational relevance to our findings. Additionally, we will determine the role of PLZF in controlling MAIT and iNKT cells ability to reside in non-lymphoid tissues and to respond swiftly to stimulation. How PLZF ultimately governs innate T cell functions will be determined using two disease models to probe the tissue-repair and anti-microbial functions of innate T cells in vivo. Altogether, this proposal brings together complementary expertise in innate T cell biology and in epigenetics to elucidate the mechanisms by which PLZF, a key transcriptional regulator, influences the development and function of major immune cell populations, both in mice and humans. Our innovative approaches may reveal the epigenetic regulation of innate T cells with unprecedented depth and resolution. Since PLZF is involved in the development of innate lymphoid cells and a subset of gdT cells, the Epi-Tinn project may identify new targets for the specific modulation of an array of immune cells with clinical relevance in humans.
