Targeting BCL2 Family in Human Myeloid Dendritic Cells: A Challenge to Cure Diseases with Chronic Inflammations Associated with Bone Loss

Figure 5

Model for the therapeutical management of diseases associated with IL-17A-dependent chronic inflammation with bone loss. In the context of IL-17A-driven inflammation, IL-17A amplifies OC formation and consequently bone resorption (see details in Figure 4). In addition, IL-17A induces BCL2A1 expression in MCL1⁺ monocyte-derived DC, DC clustering, and fusion, leading to a mixed culture, containing both mononuclear and multinuclear (GMIC) inflammatory DC. These inflammatory DC and GMIC express MCL1 and BCL2A1 contrary to OC whose survival is under the control of BCL2. Tolerogenic DCs activate regulatory T cells able to control activated Th17 cells. The question mark indicates that the status of BCL2 family in tolerogenic DC is unknown and should be studied to validate this model. In order to cure diseases with IL-17A-dependent chronic inflammation associated with bone loss, we suggest killing inflammatory DC and GMIC by targeting both MCL1 and BCL2A1. In parallel performing therapeutic autologous vaccination with tolerogenic DC may help breaking IL-17A-dependent chronic inflammation to restore normal bone physiology.