DECTIN1⁺ myeloid-derived suppressor cells mediate therapeutic effect of MSCs in haplo-HSCT for severe aplastic anemia
Abstract
Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disorder marked by pancytopenia and marrow hypoplasia. As a promising therapeutic option, haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is still limited by graft rejection and delayed immune reconstitution, which can be effectively mitigated by mesenchymal stem cell (MSC) coinfusion. Here, we demonstrated that haplo-HSCT significantly restored the proportion and immunosuppressive capacity of bone marrow myeloid-derived suppressor cells (MDSCs) in SAA patients, and DECTIN1 ⁺ MDSCs emerged as central immunoregulators. MSC coinfusion further enhanced this effect. Mechanistically, MSC-derived exosomal ANXA2 upregulated DECTIN1 expression in MDSCs, which in turn activated STAT3 signaling to increase TNFAIP3 expression, thereby suppressing inflammatory T-cell responses. These changes were also reflected in peripheral blood. Human bone marrow organoid experiments confirmed that MSC coinfusion promoted DECTIN1 ⁺ MDSC expansion and accelerated bone marrow microenvironment recovery. Our findings revealed a previously unrecognized MSC-mediated mechanism and highlighted DECTIN1 ⁺ MDSCs as key immunoregulatory mediators and potential therapeutic targets in SAA.
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BibTeX
@article{yu2026dectin1,
title = {{DECTIN1⁺ myeloid-derived suppressor cells mediate therapeutic effect of MSCs in haplo-HSCT for severe aplastic anemia}},
author = {Fu-Hao Yu and Gui-Yan Jia and Pei-Lin Li and Shuang Xia and Rui-Cong Hao and Heng-Xiang Wang and Dai-Hong Liu and Heng Zhu and Li Ding},
journal = {Communications Biology},
year = {2026},
month = nov,
doi = {10.1038/s42003-026-11246-0},
url = {https://www.nature.com/articles/s42003-026-11246-0},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - DECTIN1⁺ myeloid-derived suppressor cells mediate therapeutic effect of MSCs in haplo-HSCT for severe aplastic anemia
AU - Fu-Hao Yu
AU - Gui-Yan Jia
AU - Pei-Lin Li
AU - Shuang Xia
AU - Rui-Cong Hao
AU - Heng-Xiang Wang
AU - Dai-Hong Liu
AU - Heng Zhu
AU - Li Ding
PY - 2026
DA - 2026/11/06
JO - Communications Biology
DO - 10.1038/s42003-026-11246-0
UR - https://www.nature.com/articles/s42003-026-11246-0
AB - Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disorder marked by pancytopenia and marrow hypoplasia. As a promising therapeutic option, haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is still limited by graft rejection and delayed immune reconstitution, which can be effectively mitigated by mesenchymal stem cell (MSC) coinfusion. Here, we demonstrated that haplo-HSCT significantly restored the proportion and immunosuppressive capacity of bone marrow myeloid-derived suppressor cells (MDSCs) in SAA patients, and DECTIN1 ⁺ MDSCs emerged as central immunoregulators. MSC coinfusion further enhanced this effect. Mechanistically, MSC-derived exosomal ANXA2 upregulated DECTIN1 expression in MDSCs, which in turn activated STAT3 signaling to increase TNFAIP3 expression, thereby suppressing inflammatory T-cell responses. These changes were also reflected in peripheral blood. Human bone marrow organoid experiments confirmed that MSC coinfusion promoted DECTIN1 ⁺ MDSC expansion and accelerated bone marrow microenvironment recovery. Our findings revealed a previously unrecognized MSC-mediated mechanism and highlighted DECTIN1 ⁺ MDSCs as key immunoregulatory mediators and potential therapeutic targets in SAA.
SN - 2399-3642
ER -