Three distinct tolerogenic CD14⁺ myeloid cell types to actively manage autoimmune disease: Opportunities and...

Current treatment for patients with autoimmune disorders including rheumatoid arthritis, multiple sclerosis and type 1 diabetes, often consists of long-term drug regimens that broadly dampen immune responses. These non-specific treatments are frequently associated with severe side effects creating an urgent need for safer and more effective therapy to promote peripheral tolerance in autoimmune diseases. Cell-based immunotherapy may offer an encouraging alternative, where tolerogenic CD14⁺ myeloid cells are infused to inhibit autoreactive effector cells. In this review, we compared in depth three promising tolerogenic CD14⁺ candidates for the treatment of autoimmune disease: 1) tolerogenic dendritic cells, 2) monocytic myeloid-derived suppressor cells and 3) CD14⁺ type 2 conventional dendritic cells. TolDC-based therapy has entered clinical testing whereas evidence from the latter two cell types m-MDSCs and CD14⁺ cDC2s is predominantly coming from cancer immunology research. These three cell types have distinct cellular properties and immunosuppressive mechanisms offering unique opportunities to be explored. However, these cells differ in stage of development towards immunotherapy each facing additional hurdles. Therefore, we speculate on the potential benefits and risks of these cell types as novel cell-based immunotherapies to control autoimmune disease in patients.