Merocytic Dendritic Cells Compose a Conventional Dendritic Cell Subset with Low Metabolic Activity

• Published in: The Journal of immunology (1950) Vol. 205; no. 1; pp. 121 - 132
• Main Authors: Audiger, Cindy, Fois, Adrien, Thomas, Alyssa L, Janssen, Edith, Pelletier, Martin, Lesage, Sylvie
• Format: Journal Article
• Language: English
• Published: United States 01-07-2020
• Subjects: Animals; Clonal Anergy; Dendritic Cells - immunology; Dendritic Cells - metabolism; Female; Interferon Regulatory Factors - metabolism; Male; Mice; Mice, Transgenic; Models, Animal; Receptors, Antigen, T-Cell - genetics; RNA-Seq; Transcription Factors - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1900970

Conventional dendritic cells (cDCs) are arguably the most potent APCs that induce the activation of naive T cells in response to pathogens. In addition, at steady-state, cDCs help maintain immune tolerance. Two subsets of cDCs have been extensively characterized, namely cDC1 and cDC2, each contributing differently to immune responses. Recently, another dendritic cell (DC) subset, termed merocytic DCs (mcDCs), was defined. In contrast to both cDC1 and cDC2, mcDCs reverse T cell anergy, properties that could be exploited to potentiate cancer treatments. Yet, whether mcDCs represent an unconventional DC or a cDC subset remains to be defined. In this article, we further characterize mcDCs and find that they bear true characteristics of cDC subsets. Indeed, as for cDCs, mcDCs express the cDC-restricted transcription factor
and display very potent APC activity. In addition, mcDC population dynamics parallels that of cDC1 and cDC2 in both reconstitution kinetic studies and parabiotic mice. We next investigated their relatedness to cDC1 and cDC2 and demonstrate that mcDCs are not dependent on cDC1-related
and
transcription factors, are dependent on
, a cDC2-specific transcription factor, and express a unique transcriptomic signature. Finally, we find that cDC1, cDC2, and mcDCs all present with different metabolic phenotypes, in which mcDCs exhibit the lowest glucose uptake activity and mcDC survival is the least affected by glycolysis inhibition. Defining the properties of mcDCs in mice may help identify a functionally equivalent subset in humans leading to the development of innovative cancer immunotherapies.