Retinoic Acid-Containing Liposomes for the Induction of Antigen-Specific Regulatory T Cells as a Treatment for Autoimmune Diseases

Autor: Daniëlle ter Braake, Naomi Benne, Chun Yin Jerry Lau, Enrico Mastrobattista, Femke Broere
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Pharmaceutics, Vol 13, Iss 11, p 1949 (2021)
Druh dokumentu: article
ISSN: 13111949
1999-4923
DOI: 10.3390/pharmaceutics13111949
Popis: The current treatment of autoimmune and chronic inflammatory diseases entails systemic immune suppression, which is associated with increased susceptibility to infections. To restore immune tolerance and reduce systemic side effects, a targeted approach using tolerogenic dendritic cells (tolDCs) is being explored. tolDCs are characterized by the expression of CD11c, the major histocompatibility complex (MHC)II and low levels of co-stimulatory molecules CD40 and CD86. In this study, tolDCs were generated using a human-proteoglycan-derived peptide (hPG) and all-trans retinoic acid (RA). RA-tolDCs not only display a tolerogenic phenotype but also can induce an antigen-specific regulatory T cell (Treg) response in vitro. However, further analysis showed that RA-tolDCs make up a heterogeneous population of DCs, with only a small proportion being antigen-associated tolDCs. To increase the homogeneity of this population, 1,2-distearoyl-sn-glycero-3-phosphoglycerol (DSPG)-containing liposomes were used to encapsulate the relevant antigen together with RA. These liposomes greatly enhanced the proportion of antigen-associated tolDCs in culture. In addition, in mice, we showed that the liposomal co-delivery of antigen and RA can be a more targeted approach to induce antigen-specific tolerance compared to the injection of RA-tolDCs, and that these liposomes can stimulate the generation of antigen-specific Tregs. This work highlights the importance of the co-delivery of an antigen and immunomodulator to minimize off-target effects and systemic side effects and provides new insights in the use of RA for antigen-specific immunotherapy for autoimmune and chronic inflammatory diseases.
Databáze: Directory of Open Access Journals
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