MYC deficiency impairs the development of effector/memory T lymphocytes

Mathis Nozais; Marie Loosveld; Saran Pankaew; Clémence Grosjean; Noémie Gentil; Julie Quessada; Bertrand Nadel; Cyrille Mionnet; Delphine Potier; Dominique Payet-Bornet

doi:10.1016/j.isci.2021.102761

MYC deficiency impairs the development of effector/memory T lymphocytes

iScience. 2021 Jun 19;24(7):102761. doi: 10.1016/j.isci.2021.102761. eCollection 2021 Jul 23.

Authors

Affiliations

¹ Aix Marseille Univ, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy (CIML), Parc scientifique de Luminy, Case 906, 13288 Marseille cedex 9, France.
² APHM, Hôpital La Timone, Laboratoire d'Hématologie, Marseille, France.

Abstract

In the thymus, T cell progenitors differentiate in order to generate naive T lymphocytes which migrate in the periphery where they will fulfill their function in the adaptive immune response. During thymopoiesis, genomic alterations in thymocytes can promote leukemia development. Among recurrent alteration is PTEN inactivation, which is associated to MYC overexpression. Herein, we used conditional Pten and Myc knockout mouse models and single-cell RNA-sequencing approach, to investigate the impact of MYC loss on physio-pathological development of PTEN-proficient or PTEN-deficient T lymphocytes. First, our results confirm that MYC is mandatory for PTEN loss-mediated leukemogenesis, while it is not required for terminal steps of thymopoiesis. In contrast, we uncovered that Myc ablation in CD4⁺CD8⁺ thymocytes disrupts T lymphocytes homeostasis in the spleen, notably by drastically reducing the number of MYC-deficient effector/memory T cells. Collectively, our data show that besides naive T cells proliferation, MYC is essential for effector/memory differentiation.

Keywords: Immunology; Molecular biology; Molecular genetics.