Autoantigen-specific immune tolerance in pathological and physiological cell death: Nanotechnology comes into view

Apoptotic cells are tolerogenic and can present self-antigens in the absence of inflammation, to antigen-presenting cells by the process of efferocytosis, resulting in anergy and depletion of immune effector cells. This tolerance is essential to maintain immune homeostasis and prevent systemic autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Consequently, effective efferocytosis can result in the induction of immune tolerance mediated via triggering modulatory lymphocytes and anti-inflammatory responses. Furthermore, several distinct soluble factors, receptors and pathways have been found to be involved in the efferocytosis, which are able to regulate immune tolerance by lessening antigen presentation, inhibition of T-cell proliferation and induction of regulatory T-cells. Some newly developed nanotechnology-based approaches can induce antigen-specific immunological tolerance without any systemic immunosuppression. These strategies have been explored to reverse autoimmune responses induced against various protein antigens in different diseases. In this review, we describe some nanotechnology-based approaches for the maintenance of self-tolerance using the apoptotic cell clearance process (efferocytosis) that may be able to induce immune tolerance and treat autoimmune diseases.