Characterization of merocytic dendritic cells homeostasis

Abstract

Abstract In contrast to conventional dendritic cells (cDC), when merocytic DC (mcDC) present antigens (Ag) derived from apoptotic bodies, T cell anergy is reversed rather than induced. Although helpful to tumor clearance, reversing T cell anergy is detrimental in autoimmunity. Interestingly, mcDC are present in higher proportion in type 1 diabetes (T1D)-prone NOD mice than in B6 mice. Still, little is known about the immunological properties of mcDC that define them as a DC subset. Phenotypic characterization of mcDC revealed that they express the cDC-restricted transcription factor, Zbtb46. Moreover, we found that mcDC are potent inducers of mixed lymphocyte reactions, a key trait defining them as cDC. Investigation of other transcription factors associated with specific cDC functions, such as Irf4 and Irf8, reveal that mcDC are heterogeneous, with phenotypic and functional characteristics more closely resembling CD8α cDC. Comparative gene profiles by principal component analysis revealed that mcDC clustered more closley to CD8α cDC than other DC subsets. Still, mcDC are distinct from CD8α cDC, as mcDC are present in Batf3-deficient mice. Together, these data demonstrate that mcDC are a cDC subset with unique ability to break antigen specific tolerance. Understanding the homeostatic regulation of this new cDC subset will permit to develop new therapies for diseases, such as autoimmunity or cancer where they can be either pathogenic or beneficial.