Cellules myéloïdes et métabolisme

Our goal is to decipher the diversity, metabolic profile and functions of resident macrophages in BAT and adrenal glands.

A) Brown adipose tissue. Using single-cell RNA seq, we documented an impressive diversity in myeloid cell populations in BAT. We are working with Dr. M. Artyomov to define the developmental trajectory and metabolic configuration of each of these populations. Results obtained in this project were recently published in Nature Communications (Gallerand et al., 2021). We are currently investigating the functions of BAT macrophage subsets during tissue homeostasis and cold exposure. We developed and validated genetic models allowing to target selectively BAT macrophage subsets.

B) Adrenal Glands. The presence of F4/80+ cells was demonstrated in adrenal glands by a pioneering work in 1984. More recently, it was established that F4/80 expression was shared among several myeloid cell types including macrophages, monocytes, dendritic cells and eosinophils. Macrophages have been described in endocrine organs including pancreas, testis and ovaries. Using multiple complementary approaches, we documented the presence of several macrophage populations in adrenal glands. We observed a sex dimorphism in macrophage populations and showed that these cells are involved in the homeostasis of local hormone levels, in particular during stress exposure (Dolfi et al., Cell Reports 2022). We are currently collaborating with Dr. Jesse Williams (Minnesota, USA) on this topic.

Metabolic control of myeloid cell functions in chronic inflammatory diseases. We aim to unravel the impact of glucose metabolism on myeloid cell functions during atherosclerosis and psoriasis.

A) Atherosclerosis. Immune cell dysregulation and chronic inflammation are major causes of atherosclerotic plaque development. Importantly, myeloid cell activation is paralleled by increased glucose utilization. However, the biological significance of increased glucose incorporation in atherosclerotic plaques and the immune cell type(s) accumulating this metabolite still need to be established.

B) Psoriasis. Additionally, we are investigating the role of glucose metabolism on dendritic cell migration and IL-23 production during psoriasis and its exacerbation by fatty acids. IL-23 production by conventional dendritic cells is dependent on metabolic fluxes. We aim to decipher whether modulating glucose entry into the pentose phosphate pathway might impact on DCs migration and IL-23 production.