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Related Experiment Video

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

Mi-Ae Lyu1, Ximing Tang2, Joseph D Khoury3

  • 1Department of Lymphoma/Myeloma, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States.

Frontiers in Immunology
|September 22, 2023
PubMed
Summary

Allogeneic regulatory T cells (Tregs) from umbilical cord blood (UCB) can suppress inflammation and reduce autoantibodies in lupus nephritis (LN). This UCB-Treg therapy shows promise for treating lupus nephritis by improving kidney function and resolving organ damage.

Keywords:
albuminuriaallogeneicdsDNA antibodieslupus nephritis (LN)regulatory T cells (Tregs)systemic lupus erythematosus (SLE)umbilical cord blood (UCB)

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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.