Les cellules dendritiques mérocytiques : un nouveau sous-type de cellules dendritiques conventionnelles spécifiquement régulée par Bim
Unlike other conventional dendritic cells (cDCs) subtypes, presentation of peptides derived from apoptotic bodies by merocytic dendritic cells (mcDCs) is associated with a break of tolerance. Presentation of peptides derived from pancreatic beta cells by mcDC is linked to diabetes induction. However, when loaded with peptides derived from tumor cells, they allow the reactivation of T cells and the elimination of the tumor. These properties specific to mcDC highlight new aspects in the control of break of tolerance. Understanding their relationships with other DCs and their regulation is important for understanding the mechanisms associated with immune tolerance. We have determined that mcDCs are cDCs. mcDCs are short-lived cells able to induce an allogeneic response. They express the specific cDC transcription factor, Zbtb46. mcDCs are differentiated from the cDC common precursors. They express and require IRF-4 for their homeostasis, a transcription factor associated with cDC2 differentiation. However, the proximity of mcDC to cDC2 differs in terms of metabolism where they have different signatures. mcDCs are found in greater numbers in the mouse model of spontaneous autoimmune diabetes (NOD) than in a resistant line (C57BL/6). Our laboratory validated that the Idd13 locus of chromosome 2 was linked to mcDC number, thus suggesting that one or more genes of this locus have a role in regulating the number of mcDC. By targeting polymorphic genes between the NOD and C57BL/6 mice, we determined that Bim gene, encoding a pro-apoptotic molecule, regulate specifically mcDC in a bone marrow intrinsic manner. Therefore, mcDCs are a subset of cDCs specifically regulated by Bim. This subtype of cDCs is a key player in break of tolerance and understanding their homeostasis is important in determining their role in immune tolerance.
Bim Apoptose Conventional Dendritic Cell Merocytic dendritic cell Homeostasis Immune Tolerance Apoptosis