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  2. Mesenchymal stem cells alleviate idiopathic pneumonia syndrome by facilitating M2 polarization via CCL2/CCR2 axis and further inducing formation of regulatory CCR2 + CD4 + T cells

Mesenchymal stem cells alleviate idiopathic pneumonia syndrome by facilitating M2 polarization via CCL2/CCR2 axis and further inducing formation of regulatory CCR2 + CD4 + T cells

  • Stem Cell Res Ther. 2025 Mar 1;16(1):108. doi: 10.1186/s13287-025-04232-6.
Chao Xue 1 Wei Liu 1 Yuan Li 1 Yue Yin 1 Bo Tang 1 Jinye Zhu 1 Yujun Dong 1 Huihui Liu 2 Hanyun Ren 3
Affiliations

Affiliations

  • 1 Department of Hematology, Peking University First Hospital, 8#, Xishiku Street, Xicheng District, Beijing, 100034, PR China.
  • 2 Department of Hematology, Peking University First Hospital, 8#, Xishiku Street, Xicheng District, Beijing, 100034, PR China. huihuiliu@bjmu.edu.cn.
  • 3 Department of Hematology, Peking University First Hospital, 8#, Xishiku Street, Xicheng District, Beijing, 100034, PR China. renhy0813@163.com.
Abstract

Background: Our previous study revealed that mesenchymal stem cells (MSCs) can secrete large amounts of the chemokine CCL2 under inflammatory conditions and alleviate idiopathic pneumonia syndrome (IPS) by promoting regulatory CCR2 + CD4 + T-cell formation through the CCL2‒CCR2 axis. Given the abundance of macrophages in lung tissue, how these macrophages are regulated by MSC-based prophylaxis via IPS and their interactions with T cells in lung tissue during allo-HSCT are still not fully understood.

Methods: An IPS mouse model was established, and MSC-based prophylaxis was administered. In vitro coculture systems and an IPS model were used to study the interactions among MSCs, macrophages and T cells.

Results: Prophylactic administration of MSCs induced M2 polarization and alleviated acute graft-versus-host disease (aGVHD) and lung injury in an IPS mouse model. In vitro coculture studies revealed that M2 polarization was induced by MSC-released CCL2 and that these M2 macrophages promoted the formation of regulatory CCR2 + CD4 + T cells. Blocking the CCL2-CCR2 interaction in vitro reversed MSC-induced M2 polarization and abolished the induction of CCR2 + CD4 + T-cell formation. Additionally, in vivo administration of a CCL2 or CCR2 Antagonist in the IPS mouse model exacerbated aGVHD and lung injury, accompanied by a reduction in M2 macrophages and reduced formation of regulatory CCR2 + CD4 + T cells in lung tissue.

Conclusions: MSCs alleviate IPS by facilitating M2 polarization via the CCL2‒CCR2 axis and further inducing the formation of regulatory CCR2 + CD4 + T cells.

Keywords

Allogeneic haematopoietic stem cell transplantation; CCL2-CCR2; CCR2 + CD4 + T cells; Idiopathic pneumonia syndrome; Macrophage; Mesenchymal stem cells; Polarization.

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