Allogeneic cord blood regulatory T cells decrease dsDNA antibody and improve albuminuria in systemic lupus...

Area of Science:

• Immunology
• Nephrology
• Cell Therapy

Background:

• Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE) driven by pathogenic T cells and autoantibodies.
• Regulatory T cells (Tregs) are crucial for immune suppression but are deficient in SLE patients, correlating with disease progression.
• This study investigates the potential of allogeneic, healthy Tregs from umbilical cord blood (UCB) to counteract LN-associated inflammation and protect kidney function.

Purpose of the Study:

• To evaluate the suppressive capacity of UCB-Tregs against T cells and inflammatory cytokine production from SLE patients.
• To assess the therapeutic efficacy of UCB-Tregs in a humanized mouse model of SLE and LN.
• To determine the impact of UCB-Treg therapy on immune cell infiltration, autoantibody levels, and kidney damage.

Main Methods:

• In vitro assessment of UCB-Treg suppression of healthy donor T cells and SLE peripheral blood mononuclear cells (PBMCs), and their effect on cytokine secretion.
• Establishment of a humanized SLE mouse model by transplanting human SLE-PBMCs, followed by single or multiple UCB-Treg injections.
• Analysis of immune cell populations, cytokine levels, anti-dsDNA IgG antibodies, and kidney damage markers (albuminuria) in treated mice.

Main Results:

• UCB-Tregs effectively suppressed T cell proliferation and reduced inflammatory cytokine (IFN-γ, TNF-α, IL-6, IL-17A) secretion by SLE PBMCs in vitro, with increased IL-10 production.
• In vivo, UCB-Treg administration decreased CD8+ T effector cells and circulating inflammatory cytokines in mice.
• UCB-Treg recipients showed improved skin inflammation, reduced immune cell infiltration in organs, lower anti-dsDNA IgG levels, and decreased albuminuria.

Conclusions:

• UCB-Tregs demonstrate significant potential to mitigate inflammation, reduce autoantibody production, and ameliorate end-organ damage in SLE, particularly improving kidney function.
• Adoptive therapy using UCB-Tregs represents a promising therapeutic strategy for lupus nephritis that warrants clinical investigation.