Tolerogenic De-liver-y: Glycopolymer-mediated Approaches to Induce Antigen-specific Tolerance

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Numerous autoimmune diseases, which currently affect a sizable portion of the global population, are driven by aberrant autoantigen-specific T cell responses that result in tissue destruction and loss of function. Current therapeutics for autoimmunity are non-curative and rely on global immunosuppression, leaving patients vulnerable to opportunistic infections and malignancies. An ideal approach would suppress autoantigen-specific T cell responses while leaving the remainder of the immune system intact. Recently, Tremain et al. have developed a therapeutic strategy that suppresses autoantigen-specific T cell responses by targeting autoantigens to the liver’s innate tolerogenic environment. In their approach, antigens are modified with synthetic polymeric glycosylations that target internalizing C-type lectins on the surface of liver antigen presenting cells. Autoantigens targeted to liver antigen presenting cells are presented to autoantigen-specific T cells in the presence of immunosuppressive signals that drive T cells to undergo apoptosis, adopt a state of anergy, or differentiate into T regulatory cells—a subset of T cells that can provide durable suppression of autoantigen-specific T cell responses. This mini-review describes the mechanisms by which glycopolymer-mediated targeting of autoantigens to the liver establishes autoantigen-specific immunological tolerance, summarizes the various findings of the recent publications that utilize this platform, and discusses potential therapeutic applications for treating autoimmune diseases and allergies.