Splenic and hepatic antigen-presenting cells (APCs)

Splenic and hepatic antigen-presenting cells (APCs), specifically Kupffer cells in the liver and marginal zone macrophages in the spleen, are specialized immune cells responsible for the clearance of senescent or modified erythrocytes (Kontos et al., 2013). This physiological process is naturally non-inflammatory and tolerogenic, preventing immune responses against self-antigens on red blood cells (Grimm et al., 2015). By loading erythrocytes with antigens like Ovalbumin (OVA), researchers can direct these antigens to the tolerogenic APCs of the liver and spleen to induce systemic immune tolerance (Pishesha et al., 2021). Upon internalization, the antigens are processed and presented on MHC molecules to T cells in the absence of costimulatory signals, leading to the expansion of regulatory T cells (Tregs) and the deletion of effector T cells (Anokion, 2024). This mechanism is the basis for therapeutic platforms like Anokion's KAN-101, which targets Celiac disease by inducing tolerance to gliadin. The approach aims to treat autoimmune diseases and allergies by re-establishing immune homeostasis in an antigen-specific manner. Safety considerations include the potential for hemolysis or unintended immune activation if the delivery system is compromised.

Other names

Kupffer cellsSplenic macrophagesMarginal zone macrophagesTolerogenic antigen-presenting cells

Induction of antigen-specific immune tolerance via presentation of erythrocyte-delivered antigens by tolerogenic APCs to T cells.