The healthy immune system extinguishes infections while preserving the body’s integrity and preventing inflammatory reactions against harmless components through mechanisms of immune tolerance.
Autoimmune diseases and allergies are conditions when immune tolerance fails.
Most current treatments suppress immune cells irrespective of the components they recognize (their specific antigens), thereby compromising the defense against infection and immune surveillance, as well. A key advantage of antigen-specific immune tolerance induction (such as the Topas approach) is the potential to target specifically the pathogenic immune reactions while sparing desired immunity.
Liver sinusoidal endothelial cells (LSECs) are constantly exposed to blood borne (e.g. gut-derived), mostly harmless antigens that they take up and present effectively to T cells, a central type of immune cell.
Given the need to induce and preserve tolerance to innocuous antigens, LSECSs are poised to promote immune tolerance. Through their ability to activate a key anti-inflammatory mediator (latent TGF-β) on their surface, LSECs support the induction of anti-inflammatory regulatory T cells (Tregs), a critically important type of immune cell for maintaining immune tolerance.