Activation, Amplification, and Ablation as Dynamic Mechanisms of Dendritic Cell Maturation

SIMPLE SUMMARY: The maturation of dendritic cells, potent antigen-presenting cells of the immune system, determines the fundamental ability of these cells to initiate specific responses by T cells, which are key effector cells of the adaptive immune system. Maturation is a dynamic process that is highly sensitive to specific stimuli. As the individual cellular and molecular pathways contributing to maturation are still being uncovered, an in-depth understanding of how these various mechanisms are integrated to produce specific functional outcomes remains elusive. Here, we discuss the emerging paradigm encompassing several biologically distinct mechanisms that are functionally integrated into the process of maturation. ABSTRACT: T cell responses to cognate antigens crucially depend on the specific functionality of dendritic cells (DCs) activated in a process referred to as maturation. Maturation was initially described as alterations of the functional status of DCs in direct response to multiple extrinsic innate signals derived from foreign organisms. More recent studies, conducted mainly in mice, revealed an intricate network of intrinsic signals dependent on cytokines and various immunomodulatory pathways facilitating communication between individual DCs and other cells for the orchestration of specific maturation outcomes. These signals selectively amplify the initial activation of DCs mediated by innate factors and dynamically shape DC functionalities by ablating DCs with specific functions. Here, we discuss the effects of the initial activation of DCs that crucially includes the production of cytokine intermediaries to collectively achieve amplification of the maturation process and further precise sculpting of the functional landscapes among DCs. By emphasizing the interconnectedness of the intracellular and intercellular mechanisms, we reveal activation, amplification, and ablation as the mechanistically integrated components of the DC maturation process.