Nanoparticle-mediated Delivery of IL-2 To T Follicular Helper Cells Protects BDF1 Mice from Lupus-like Disease

Concetta Ferretti; David A Horwitz; Sean Bickerton; Antonio La Cava

doi:10.2478/rir-2021-0024

Nanoparticle-mediated Delivery of IL-2 To T Follicular Helper Cells Protects BDF1 Mice from Lupus-like Disease

Rheumatol Immunol Res. 2021 Dec 15;2(3):185-193. doi: 10.2478/rir-2021-0024. eCollection 2021 Sep.

Authors

Concetta Ferretti¹, David A Horwitz^{2

3}, Sean Bickerton⁴, Antonio La Cava^{1

5}

Affiliations

¹ Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
² Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
³ General Nanotherapeutics, Santa Monica, CA, USA.
⁴ Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
⁵ Dipartimento di Biochimica e. Biotecnologie Mediche, University of Naples Federico II, Naples, Italy.

Abstract

We recently reported that poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) loaded with interleukin (IL)-2 and targeted to T cells inhibited the development of lupus-like disease in BDF1 mice by inducing functional T regulatory cells (Tregs). Here we show that the protection from disease and the extended survival of BDF1 mice provided by IL-2-loaded NPs targeted to T cells is not only due to an induction of Tregs but also contributed by an inhibition of T follicular helper (T_FH) cells. These results identify a dual protective activity of IL-2 in the control of lupus autoimmunity, namely the inhibition of effector T_FH cells, in addition to the previously known induction of Tregs. This newly recognized activity of IL-2 delivered by NPs can help better explain the beneficial effects of low-dose IL-2 immunotherapy in systemic lupus erythematosus (SLE), and might be considered as a new strategy to slow disease progression and improve outcomes in lupus patients.

Keywords: T cells; T follicular helper (TFH) cells; autoimmunity; systemic lupus erythematosus.