CAR immunotherapy in autoimmune diseases: promises and challenges.

In recent years, the use of chimeric antigen receptor (CAR)-T cells has emerged as a promising immunotherapy in multiple diseases. CAR-T cells are T cells genetically modified to express a surface receptor, known as CAR, for the targeting of cognate antigens on specific cells. The effectiveness of CAR-T cell therapy in hematologic malignancies including leukemia, myeloma, and non-Hodgkin's lymphoma has led to consider its use as a potential avenue of treatment for autoimmune diseases.

Nanoparticles loaded with IL-2 and TGF-β promote transplantation tolerance to alloantigen.

We have previously reported that nanoparticles (NPs) loaded with IL-2 and TGF-β and targeted to T cells induced polyclonal T regulatory cells (Tregs) that protected mice from graft-versus-host disease (GvHD). Here, we evaluated whether administration of these NPs during alloantigen immunization could prevent allograft rejection by converting immunogenic responses to tolerogenic ones. Using C57BL/6 mice and BALB/c mice as either donors or recipients of allogeneic splenocytes, we found that treatment with the tolerogenic NPs in both strains of mice resulted in a marked inhibition of mixed lymphocyte reaction (MLR) to donor cell alloantigen but not to third-party control mouse cells after transfer of the allogeneic cells.

Adeno-Associated Virus Type 5 Infection via PDGFRα Is Associated With Interstitial Lung Disease in Systemic Sclerosis and Generates Composite Peptides and Epitopes Recognized by the Agonistic Immunoglobulins Present in Patients With Systemic Sclerosis.

Objective: The etiopathogenesis of systemic sclerosis (SSc) is unknown. Platelet-derived growth factor receptors (PDGFRs) are overexpressed in patients with SSc. Because PDGFRα is targeted by the adeno-associated virus type 5 (AAV5), we investigated whether AAV5 forms a complex with PDGFRα exposing epitopes that may induce the immune responses to the virus-PDGFRα complex.

Low-dose interleukin-2 therapy in systemic lupus erythematosus.

In systemic lupus erythematosus (SLE), T regulatory cells (T) contribute to the inhibition of autoimmune responses by suppressing self-reactive immune cells. Interleukin (IL)-2 plays an essential role in the generation, function and homeostasis of the T and is reduced in SLE. Several clinical studies, including randomized trials, have shown that low-dose IL-2 therapy in SLE patients is safe and effective and can reduce disease manifestations.

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

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) cells. These results identify a dual protective activity of IL-2 in the control of lupus autoimmunity, namely the inhibition of effector T cells, in addition to the previously known induction of Tregs.

MIS-C: A COVID-19-as sociated condition between hypoimmunity and hyperimmunity.

Multisystem inflammatory syndrome in children (MIS-C) is a rare, severe complication of COVID-19. A better knowledge of immunological, cellular, and genetic characteristics of MIS-C could help better understand the pathogenesis of the disease and contribute to identifying specific diagnostic biomarkers and develop targeted therapies. We studied 37 MIS-C children at hospital admission and 24 healthy controls analyzing serum cytokines (IFN-α, IFN-β, IFN-γ, IL-6, IL-10, IL-17A, IL-12p70 and TNF), lymphocyte populations by flow cytometry and 386 genes related to autoimmune diseases, autoinflammation and primary immunodeficiencies by NGS.

Improved outcomes in rheumatoid arthritis with obesity after a weight loss intervention: randomized trial.

Objective: To examine whether a weight loss intervention programme improves RA disease activity and/or musculoskeletal ultrasound synovitis measures in obese RA patients.

Methods: We conducted a proof-of-concept, 12-week, single-blind, randomized controlled trial of obese RA patients (BMI ≥ 30) with 28-joint DAS (DAS28)  ≥ 3.2 and with evidence of power Doppler synovitis.

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

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.

Nanoparticles Engineered as Artificial Antigen-Presenting Cells Induce Human CD4 and CD8 Tregs That Are Functional in Humanized Mice.

Artificial antigen-presenting cells (aAPCs) are synthetic versions of naturally occurring antigen-presenting cells (APCs) that, similar to natural APCs, promote efficient T effector cell responses . This report describes a method to produce acellular tolerogenic aAPCs made of biodegradable poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) and encapsulating IL-2 and TGF-β for a paracrine release to T cells. We document that these aAPCs can induce both human CD4 and CD8 T cells to become FoxP3 T regulatory cells (Tregs).

The pleiotropic roles of leptin in metabolism, immunity, and cancer.

The discovery of the archetypal adipocytokine leptin and how it regulates energy homeostasis have represented breakthroughs in our understanding of the endocrine function of the adipose tissue and the biological determinants of human obesity. Investigations on leptin have also been instrumental in identifying physio-pathological connections between metabolic regulation and multiple immunological functions. For example, the description of the promoting activities of leptin on inflammation and cell proliferation have recognized the detrimental effects of leptin in connecting dysmetabolic conditions with cancer and with onset and/or progression of autoimmune disease.

Systemic Lupus Erythematosus and Coronavirus Disease 2019.

Coronavirus disease 2019 (COVID-19) is a contagious infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It manifests with variable clinical pictures ranging from asymptomatic to mild or uncomplicated illness to severe disease with possible multi-organ involvement, with respiratory and vascular systems being the most often affected. Since COVID-19 can affect patients with autoimmune rheumatic conditions, the concomitant presence of two diseases may have clinical characteristics whose knowledge may help facilitate clinical management.

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

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)F (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.

DNA vaccine encoding heat shock protein 90 protects from murine lupus.

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the presence of autoantibodies to multiple self-antigens, including heat shock proteins (HSP). Because of the increased expression of HSP90 and abnormal immune responses to it in SLE, we investigated whether an HSP90 DNA vaccine could modulate the development and clinical manifestations of SLE in lupus-prone mice.

Methods: (NZB x NZW)F (NZB/W) mice were vaccinated with DNA constructs encoding HSP90 or control plasmids or vehicle.

Serafino Zappacosta: An Enlightened Mentor and Educator.

With this article, the authors aim to honor the memory of Serafino Zappacosta, who had been their mentor during the early years of their career in science. The authors discuss how the combination of Serafino Zappacosta's extraordinary commitment to teaching and passion for science created a fostering educational environment that led to the creation of the "." The review also illustrates how the research on the MHC and the inspirational scientific context in the Zappacosta's laboratory influenced the authors' early scientific interests, and subsequent professional work as immunologists.

DNA Vaccination With Hsp70 Protects Against Systemic Lupus Erythematosus in (NZB × NZW)F1 Mice.

Objective: To address whether a targeted modulation of the abnormal expression of Hsp70 and autoantibodies against this molecule in systemic lupus erythematosus can influence disease.

Methods: Lupus-prone (NZB × NZW)F1 mice that had been DNA-vaccinated with plasmids encoding Hsp70 and controls were monitored for lupus disease parameters including anti-double stranded DNA (anti-dsDNA) autoantibodies and cytokines using enzyme-linked immunosorbent assay, and for kidney function and pathology. The phenotypic and numerical changes in relevant immune cells were evaluated by flow cytometry, and cell function was assessed.

Rebalancing Immune Homeostasis to Treat Autoimmune Diseases.

During homeostasis, interactions between tolerogenic dendritic cells (DCs), self-reactive T cells, and T regulatory cells (Tregs) contribute to maintaining mammalian immune tolerance. In response to infection, immunogenic DCs promote the generation of proinflammatory effector T cell subsets. When complex homeostatic mechanisms maintaining the balance between regulatory and effector functions become impaired, autoimmune diseases can develop.

The Influence of Diet and Obesity on Gene Expression in SLE.

This review provides an overview of the known effects of diet, obesity, and the intake of different nutrients on systemic lupus erythematosus (SLE). It summarizes and discusses the studies in rodents that identified how different diets can regulate gene expression in the disease, together with a description of the effects of diet on lupus patients' inflammatory state and disease severity. The identification of selected dietary candidates that can modulate SLE onset and progression is analyzed in relation to possible targeted approaches that could ultimately ameliorate the management and prognosis of this disease.

Human T cell repertoire: what happens in thymus does not stay in thymus.

The T cell receptor (TCR) repertoire is diverse, thus allowing recognition of a wide range of pathogens by T cells. In humans, the study of the formation of TCR repertoires is problematic because of the difficulty in performing investigations in vivo. In this issue of the JCI, Khosravi-Maharlooei and colleagues describe a new humanized mouse model that allows direct investigations on this topic.