Tolerogenic dendritic cell vaccines to treat autoimmune diseases: Can the unattainable dream turn into reality?

Engineering antigen-specific immunological tolerance

“…The text in the section above focused on the T cell; on the other side of the immune synapse, DCs also dictate negative selection of auto-reactive T cells and induce Treg differentiation, and their adoptive transfer has been used to restore immune tolerance. Immature DCs cultured in vitro in the presence of antigen and immunosuppressive drugs such as vitamin D, rapamycin, or dexamethasone, develop tolerogenic properties once injected in vivo such that they have been shown to restore immune tolerance in several mouse models of autoimmunity [42 ]. Dendritic cell immunotherapy is currently in clinical trials of type 1 diabetes (ClinicalTrials.gov Identifier: NCT02354911), rheumatoid arthritis (ClinicalTrials.gov Identifier: NCT01352858), and asthma (ClinicalTrials.gov Identifier: NCT01711593).…”

Vitamin D immunoregulation through dendritic cells

“…These cells also possess decreased densities of the co‐stimulatory molecules CD80 and CD86 and of the antigen‐presenting MHCII complex 20, 23. Hence, with all three pillars of T‐cell activation being hampered by 1,25‐OH‐VD3 modulation of moDC development, its potential as a tolerance‐inducing agent for DC therapy, and as a therapeutic immune modulator against diseases with underlying inappropriate or overwhelming inflammation, was recognized 11, 18…”

“…As such, DC therapy has successfully entered the clinic for cancers,10 where cytotoxic T cells are primed by DC differentiated from easily available circulating CD14 + blood monocytes by ex vivo incubation with the tumour antigen PAP fused to granulocyte–macrophage colony‐stimulating factor (GM‐CSF). Similarly, the feasibility of DC‐based immunomodulation is being explored in the setting of autoimmune diseases, where detrimental immune reactions damage host tissue 11. Clearly, a tolerogenic approach that limited or aborted T‐cell or B‐cell responses to self antigens would represent a significant advance in the treatment or prevention of autoimmune disease.…”

Dendritic cells in atherosclerotic inflammation: the complexity of functions and the peculiarities of pathophysiological effects

“…DCs are thought nowadays as a valuable instrument for atherosclerosis immunotherapy (Van Vré et al, 2011; Takeda et al, 2012; Grassia et al, 2013; Van Brussel et al, 2013, 2014). DCs could also induce tolerance against antigens that are innate to the body (Steinman et al, 2003; Palucka and Banchereau, 2012).…”

“…Although the idea to use of DCs for vaccination in atherosclerosis is widely discussed (de Jager and Kuiper, 2011; Van Vré et al, 2011; Cheong and Choi, 2012; Döring and Zernecke, 2012; Takeda et al, 2012; Van Brussel et al, 2013, 2014), experimental studies that already utilized DCs for immunotherapy of atherosclerosis are still quite limited (Habets et al, 2010; Hjerpe et al, 2010; van Es et al, 2010; Hermansson et al, 2011; Pierides et al, 2013). Currently, an immunotherapeutic strategy based on the isolation of autologous DCs, subsequent loading with appropriate antigen(s) ex vivo (e.g., immunogenic epitopes of modified LDL or a total plaque extract), and return to the host blood is under development (Habets et al, 2010; Hjerpe et al, 2010; van Es et al, 2010; Hermansson et al, 2011; Pierides et al, 2013) (Table 1).…”