Anti-CD2 Antibody-Coated Nanoparticles Containing IL-2 Induce NK Cells That Protect Lupus Mice via a TGF-β-Dependent Mechanism.

David A Horwitz,Antonio La Cava,Tarek M Fahmy,Aijing Liu,Giuseppe Castaldo,Sean Bickerton,Giuseppe Matarese

doi:10.3389/fimmu.2020.583338

Abstract

We recently reported that the treatment with nanoparticles (NPs) loaded with tolerogenic cytokines suppressed the manifestations of lupus-like disease induced by the transfer of donor CD4+ T cells from DBA/2 mice into (C57BL/6 × DBA/2)F1 (BDF1) mice. Although the protective effects were ascribed to the induction of adaptive CD4+ and CD8+ T regulatory cells, the results suggested that another population of immune cells could be involved. Here we report that NK cells critically contribute to the protection from lupus-like disease conferred by NPs to BDF1 mice, and that this effect is TGF-β-dependent.

Highlights

Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease characterized by dysregulated immune responses that impair the mechanisms of peripheral immune tolerance that normally keep self-reactive immune cells under control [1]
We recently reported that the treatment with nanoparticles (NPs) loaded with tolerogenic cytokines suppressed the manifestations of lupus-like disease induced by the transfer of donor CD4+ T cells from DBA/2 mice into (C57BL/6 × DBA/2)F1 (BDF1) mice
To investigate possible contributions of NK cells to the protective effects conferred by the NPs in BDF1 mice, we repeated the experiment of prevention of lupus-like disease induced by IL-2/transforming growth factor b (TGF-b)-loaded NPs [10] but this time we depleted the circulating NK cells in the NP-treated animals

Summary

Introduction

Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease characterized by dysregulated immune responses that impair the mechanisms of peripheral immune tolerance that normally keep self-reactive immune cells under control [1]. A significant contribution to the unbalanced immune homeostasis in SLE derives from a dysregulated production of cytokines, e.g. insufficient amounts of circulating anti-inflammatory cytokines and a preponderance of proinflammatory cytokines. In this context, interleukin‐2 (IL‐2) and transforming growth factor b (TGF-b) are deficient in SLE, and these cytokines play critical roles in immunoregulatory responses such as the induction and maintenance of CD4+ and CD8+ T regulatory cells (Tregs) [2,3,4,5]. We show that a key contribution to the suppression of lupus-like disease in BDF1 mice by NPs comes from NK cells and their TGF-b production

Methods

Results

Conclusion