Strategies to Use Nanoparticles to Generate CD4 and CD8 Regulatory T Cells for the Treatment of SLE and Other Autoimmune Diseases.

David A Horwitz,Antonio La Cava,Sean Bickerton

doi:10.3389/fimmu.2021.681062

Abstract

Autoimmune diseases are disorders of immune regulation where the mechanisms responsible for self-tolerance break down and pathologic T cells overcome the protective effects of T regulatory cells (Tregs) that normally control them. The result can be the initiation of chronic inflammatory diseases. Systemic lupus erythematosus (SLE) and other autoimmune diseases are generally treated with pharmacologic or biological agents that have broad suppressive effects. These agents can halt disease progression, yet rarely cure while carrying serious adverse side effects. Recently, nanoparticles have been engineered to correct homeostatic regulatory defects and regenerate therapeutic antigen-specific Tregs. Some approaches have used nanoparticles targeted to antigen presenting cells to switch their support from pathogenic T cells to protective Tregs. Others have used nanoparticles targeted directly to T cells for the induction and expansion of CD4+ and CD8+ Tregs. Some of these T cell targeted nanoparticles have been formulated to act as tolerogenic artificial antigen presenting cells. This article discusses the properties of these various nanoparticle formulations and the strategies to use them in the treatment of autoimmune diseases. The restoration and maintenance of Treg predominance over effector cells should promote long-term autoimmune disease remission and ultimately prevent them in susceptible individuals.

Highlights

A major unmet need in chronic immune-mediated inflammatory diseases that include autoimmune diseases, graft versus host disease and allograft graft rejection is to achieve long-term remission
Instead, homeostasis becomes dysregulated and immunogenic dendritic cells (DCs) enable pathogenic T effector cells to predominate over the T regulatory cells (Tregs) [1]
We focus here on the application of nanoparticles in the size range 100-500 nm (Figure 1)

Summary

Introduction

A major unmet need in chronic immune-mediated inflammatory diseases that include autoimmune diseases, graft versus host disease and allograft graft rejection is to achieve long-term remission. In addition to mouse cells, tolerogenic aAPC NPs containing IL-2 and TGF-b have induced human CD4+ and CD8+ cells become Foxp3+ Tregs that were functional both in vitro and modulated systemic autoimmunity in humanized NOD/SCID immunodeficient mice.

Results

Conclusion