Macrophage migration inhibitory factor is overproduced through EGR1 in TET2low resting monocytes - Sorbonne Université
Article Dans Une Revue Communications Biology Année : 2022

Macrophage migration inhibitory factor is overproduced through EGR1 in TET2low resting monocytes

Bouchra Badaoui
Raphael Itzykson

Résumé

Somatic mutation in TET2 gene is one of the most common clonal genetic events detected in age-related clonal hematopoiesis as well as in chronic myelomonocytic leukemia (CMML). In addition to being a pre-malignant state, TET2 mutated clones are associated with an increased risk of death from cardiovascular disease, which could involve cytokine/chemokine overproduction by monocytic cells. Here, we show in mice and in human cells that, in the absence of any inflammatory challenge, TET2 downregulation promotes the production of MIF (macrophage migration inhibitory factor), a pivotal mediator of atherosclerotic lesion formation. In healthy monocytes, TET2 is recruited to MIF promoter and interacts with the transcription factor EGR1 and histone deacetylases. Disruption of these interactions as a consequence of TET2 -decreased expression favors EGR1-driven transcription of MIF gene and its secretion. MIF favors monocytic differentiation of myeloid progenitors. These results designate MIF as a chronically overproduced chemokine and a potential therapeutic target in patients with clonal TET2 downregulation in myeloid cells.
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Dates et versions

hal-03560437 , version 1 (07-02-2022)

Identifiants

Citer

Elodie Pronier, Aygun Imanci, Dorothée Selimoglu-Buet, Bouchra Badaoui, Raphael Itzykson, et al.. Macrophage migration inhibitory factor is overproduced through EGR1 in TET2low resting monocytes. Communications Biology, 2022, 5 (1), pp.110. ⟨10.1038/s42003-022-03057-w⟩. ⟨hal-03560437⟩
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