2. Academic Validation
  3. Mesenchymal stromal cells relieved systemic lupus erythematosus via CCL2 dependent macrophage polarization

Mesenchymal stromal cells relieved systemic lupus erythematosus via CCL2 dependent macrophage polarization

  • Cell Immunol. 2025 Dec:418:105046. doi: 10.1016/j.cellimm.2025.105046.
Xin Wen 1,  Genhong Yao 2,  Yujie Zhou 3,  Shanshan Liu 4,  Lingyun Sun 2
Affiliations

Affiliations

  • 1 Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, China Pharmaceutical University, Nanjing 210008, China; Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.
  • 2 Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.
  • 3 Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, China Pharmaceutical University, Nanjing 210008, China; Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China. Electronic address: [email protected].
  • 4 Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China. Electronic address: [email protected].
PMID: 41187528 DOI: 10.1016/j.cellimm.2025.105046
Abstract

Systemic lupus erythematosus (SLE) was an autoimmune disease leading to high morbidity and mortality without effective and low-side effect conventional drugs. Our previous clinical studies demonstrated umbilical cord derived mesenchymal stromal cells (MSCs) were a safe and effective treatment, but its therapeutic mechanism is still unclear. In this study, we first observed clinical used MSCs exhibited higher CCL2 expression than primary and aged MSCs, and abnormal bone marrow derived MSC (BM-MSC) from SLE patients performed decreased CCL2 expression compared to healthy control. Then, we constructed CCL2-deficient MSCs, and found the immunosuppressive activity of CCL2-deficient MSCs was impaired in the peripheral blood mononuclear cell (PBMC) inhibitory assay in vitro. CCL2-deficient MSCs also failed to relieve SLE in MRL/lpr and pristine-induced mice. To further explore the role of CCL2 in MSC therapy, we performed transcriptomic profiling of CCL2-deficient MSCs and MSCs, and identified the differential expressed genes were related to chemotaxis, including monocyte chemotaxis. Subsequently, we found that MSCs restored the imbalance in M1/M2 macrophage polarization via CCL2 in vitro. These findings provided valuable insight for investigating the therapeutic mechanism of MSC on SLE.

Keywords

CCL2; Macrophage; Mesenchymal stromal cells; Systemic lupus erythematosus.

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