Skip to Main content Skip to Navigation
Journal articles

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

Abstract : 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.
Document type :
Journal articles
Complete list of metadata

https://hal.sorbonne-universite.fr/hal-03560437
Contributor : Gestionnaire HAL-SU Connect in order to contact the contributor
Submitted on : Monday, February 7, 2022 - 3:37:10 PM
Last modification on : Wednesday, March 16, 2022 - 3:26:05 AM

File

s42003-022-03057-w.pdf
Publication funded by an institution

Identifiers

Citation

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, Nature Publishing Group, 2022, 5 (1), pp.110. ⟨10.1038/s42003-022-03057-w⟩. ⟨hal-03560437⟩

Share

Metrics

Record views

93

Files downloads

13