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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1449693
This article is part of the Research Topic The Pivotal Role of Cytokines in Autoimmune Diseases View all 8 articles

Ruxolitinib synergizes with regulatory T cells to improve inflammation but has no added benefits in decreasing albuminuria in SLE

Provisionally accepted
Mi-Ae Lyu Mi-Ae Lyu 1Ximing Tang Ximing Tang 1Maria Gabriela Raso Maria Gabriela Raso 1Meixian Huang Meixian Huang 1KE ZENG KE ZENG 1Tara Sadeghi Tara Sadeghi 2Christopher R Flowers Christopher R Flowers 1Simrit Parmar Simrit Parmar 1*
  • 1 University of Texas MD Anderson Cancer Center, Houston, United States
  • 2 Cellenkos Inc., Houston, Texas, United States

The final, formatted version of the article will be published soon.

    Background: Umbilical cord blood (UCB) derived CD4+CD25+CD127low regulatory T cells (Tregs) can decrease albuminuria and dsDNA IgG in systemic lupus erythematosus (SLE). Ruxolitinib, a JAK/STAT inhibitor, has been shown to improve cutaneous manifestations of SLE. We hypothesize that addition of ruxolitinib to UCB-Tregs may improve SLE outcomes. Methods: In vitro cell suppression assay, IL-10 secretion assay and cytokine levels in co-culture supernatants were performed to quantify impact of adding ruxolitinib to UCB-Tregs. Xenogeneic SLE model was utilized to study their in vivo combination. Results: In a dose-dependent manner, ruxolitinib addition synergizes with UCB-Tregs to suppress SLE-PBMC proliferation, inhibit CD8+ T cells and reduce phosphorylation of STAT3/STAT5/AKT in CD8+ T cells. UCB-Treg and ruxolitinib combination also down-regulates soluble form of inflammatory cytokines including IFN-, IP-10, TNF-, IL-6, sCD40L, IL-17A, IL-17F, IL-1α, and LIF in co-cultures. Addition of ruxolitinib increases UCB-Treg cell persistence in peripheral blood in vivo and decreases soluble form of human inflammatory cytokines including IFN-, TNF-, and sCD40L in plasma along with improvement of skin lesions in SLE xenografts. Compared to control, a significantly lesser CD3+, CD4+, CD8+, Ki-67+ infiltrates are observed in the lung and kidney of UCB-Tregs and/or ruxolitinib recipients. No added benefit of addition of ruxolitinib is observed on the significant improvement in the urine albumin/creatinine ratio and the anti-dsDNA IgG levels induced by UCB-Tregs. Conclusions: Our results demonstrate that addition of ruxolitinib to UCB-Tregs increases UCB-Tregs suppressor function and their persistence in vivo; down-regulate systemic inflammation and control cutaneous SLE but does not add to UCB-Treg mediated improvement in renal manifestations.

    Keywords: adoptive cell therapy, Regulatory T cells (Tregs), Allogeneic, Umbilical Cord Blood (UCB), Ruxolitinib, combination treatment, Inflammation, systemic lupus erythematosus (SLE)

    Received: 15 Jun 2024; Accepted: 10 Jan 2025.

    Copyright: © 2025 Lyu, Tang, Raso, Huang, ZENG, Sadeghi, Flowers and Parmar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Simrit Parmar, University of Texas MD Anderson Cancer Center, Houston, United States

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