2. Academic Validation
  3. MSC transplantation ameliorates depression in lupus by suppressing Th1 cell-shaped synaptic stripping

MSC transplantation ameliorates depression in lupus by suppressing Th1 cell-shaped synaptic stripping

  • JCI Insight. 2025 Mar 6;10(8):e181885. doi: 10.1172/jci.insight.181885.
Xiaojuan Han 1 2,  Dandan Wang 1 2,  Liang Chen 3,  Hua Song 2,  Xiulan Zheng 4,  Xin Zhang 2,  Shengnan Zhao 2,  Jun Liang 2,  Tianshu Xu 5,  Zhibin Hu 6 7,  Lingyun Sun 1 8
Affiliations

Affiliations

  • 1 Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China.
  • 2 Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
  • 3 Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  • 4 School of Pharmacy, Macau University of Science and Technology, Macau, China.
  • 5 Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China.
  • 6 State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China.
  • 7 Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
  • 8 Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
PMID: 40048256 DOI: 10.1172/jci.insight.181885
Abstract

Systemic lupus erythematosus (SLE), an autoimmune disease, can cause psychiatric disorders, particularly depression, via immune activation. Human umbilical cord mesenchymal stromal cell (hUCMSC) transplantation (MSCT) has been shown to ameliorate immune dysfunction in SLE by inducing immune tolerance. However, whether MSCT can relieve the depressive symptoms in SLE remains incompletely understood. Here, we demonstrate that MSCT relieved early-onset depression-like behavior in both genetically lupus-prone (MRL/lpr) and pristane-induced lupus mice by rescuing impaired hippocampal synaptic connectivity. Transplanted hUCMSCs targeted Th1 cell-derived IFN-γ to inhibit neuronal JAK/STAT1 signaling and downstream CCL8 expression, reducing phagocytic microglia apposition to alleviate synaptic engulfment and neurological dysfunction in young (8-week-old) lupus mice. Systemic delivery of exogenous IFN-γ blunted MSCT-mediated alleviation of synaptic loss and depressive behavior in lupus mice, suggesting that the IFN-γ/CCL8 axis may be an effective therapeutic target and that MSCT is a potential therapy for lupus-related depression. In summary, transplanted hUCMSCs can target systemic immunity to ameliorate psychiatric disorders by rescuing synaptic loss, highlighting the active role of neurons as intermediaries between systemic immunity and microglia in this process.

Keywords

Autoimmune diseases; Autoimmunity; Depression; Immunotherapy; Inflammation; Neuroscience.

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