Abstract
In autoimmune diseases such as multiple sclerosis (MS), disruption of the immune system's ability to balance the elimination of invading pathogens and tolerance of self-antigens leads to an attack on the body's own cell structures, in this case, myelin. A promising treatment approach is to re-educate the unbalanced immune system and re-induce tolerance of the affected self-antigen using tolerogenic dendritic cells (tolDCs). While the potential of tolDCs to downmodulate pro-inflammatory pathogenic responses in MS has been recognized, their mode of action remains largely elusive. Recent studies have shed light on the relevance of metabolic pathways in the activation, proliferation, fate, and function of immune cells, thereby playing an important role in shaping immune responses. By manipulating metabolic pathways via the microenvironment in which cells are cultured, immune cells can be re-educated in vivo towards a more tolerogenic phenotype to temper ongoing autoimmune activation. Although the effects of the metabolic microenvironment on conventional DCs (convDCs) have been well studied, similar studies on tolDCs are limited. Here, we hypothesize that the immunoregulatory effect of tolDCs can be shaped by adjusting the microenvironment during cell culture. In doing so, we aim to increase the conversion rate of monocytes into tolDCs and optimize the manufacturing procedure to ultimately scale out the process.
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