New findings highlight targeting of dendritic cells (DCs) with antigen-containing liposomes as a promising strategy for inducing autoantigen-specific immunological tolerance in autoimmune diseases. “Our data show that immune regulation could be restored in inflammatory autoimmune diseases where autoantigen is widely expressed — in models of rheumatoid arthritis (RA) and renal vasculitis,” reports corresponding author Ranjeny Thomas.

Credit: Springer Nature Limited

“Liposomes have an established clinical track record for targeted drug delivery and provide a platform for co-delivery to DCs of the lipophilic NF-κB inhibitor calcitriol with hydrophilic antigenic peptide,” says Thomas. “Importantly, co-delivery of antigen in the liposomes ensures that immune regulation is antigen-specific and not generalized,” explains Thomas.

Indeed, calcitriol-containing liposomes suppressed the cytokine-secreting and antigen-presenting capacity of DCs in vitro. In mice immunized with an antigenic peptide, administration of liposomes containing both calcitriol and the peptide suppressed the expansion of antigen-specific effector T cells and promoted the expansion of antigen-specific regulatory T cells.

An important question was whether an inflammatory setting could inhibit the induction of tolerance by activating DCs. “We show that active inflammation actually supported tolerance induction with liposomes encapsulating peptide and calcitriol,” reports Thomas. “Inflammation promoted PDL1 expression by DCs, PDL1+ DCs were more likely to take up the liposomes and PDL1 was required for the induction of regulatory T cells.”

In mouse models of RA and Goodpasture’s vasculitis (also known as anti-glomerular basement membrane disease), liposomes containing calcitriol and disease-associated peptides inhibited the development of autoimmunity and also suppressed existing disease. Analysis using peptide–MHC class II tetramer staining to visualize the autoreactive CD4+ T cell compartment suggested that liposomal treatment decreased disease severity in an antigen-specific manner.

liposomal treatment decreased disease severity in an antigen-specific manner

“The research opens up new potential for drug development and trials in patients with autoimmune diseases and in individuals at high risk of disease development,” concludes Thomas.