2B9-Fc Ameliorates Immune Thrombocytopenia by Suppressing STAT1-Mediated M1 Macrophage Polarization and Expanding Regulatory T Cells
5 affiliations
- 1Hengyang Medical College, University of South China, Hengyang 421001, China
- 2Academy of Military Medical Sciences, Beijing 100850, China
- 3State Key Laboratory of National Security Specially Needed Medicines, Beijing 100850, China
- 4College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China
- 5School of Pharmacy, Bengbu Medical University, Bengbu 233030, China
Abstract
Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder in which enhanced platelet destruction and impaired platelet production coexist, and a substantial proportion of patients remain refractory to available therapies. Here, we evaluated 2B9-Fc, a thrombopoietin (TPO) mimetic peptide engineered from a cyclic peptide with high affinity for both human and mouse c-MPL, in passive (anti-CD41 monoclonal antibody R300) and active (guinea pig anti-mouse platelet serum, GP-APS) immunization male C57BL/6J and humanized c-MPL receptor transgenic mouse models of ITP. 2B9-Fc (500 μg/kg, subcutaneously) significantly elevated peripheral platelet counts in both models (p < 0.01), without affecting WBC, RBC, or hemoglobin, and alleviated skin purpura and bleeding scores in the active model. In addition, 2B9-Fc treatment was associated with a reduced splenic M1/M2 macrophage ratio, increased regulatory T cells (Tregs), downregulated IL-6 and iNOS while upregulating TGF-β1 and Foxp3, and suppressed STAT1 phosphorylation. In humanized c-MPL receptor transgenic (MT) mice, 2B9-Fc promoted CD41+ megakaryocyte generation in vitro and sustained platelet recovery in vivo through day 14. These results indicate that 2B9-Fc ameliorates ITP and is associated with promotion of megakaryocyte maturation and restoration of immune tolerance, likely involving inhibition of STAT1-mediated M1 polarization and Treg expansion, supporting its potential for clinical translation.
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BibTeX
@article{yang20262b9fc,
title = {{2B9-Fc Ameliorates Immune Thrombocytopenia by Suppressing STAT1-Mediated M1 Macrophage Polarization and Expanding Regulatory T Cells}},
author = {Shuran Yang and Shuang Xing and Xing Shen and Wanlu Zhu and Mengting Ge and He Xiao and Kaikai Yu and Zuyin Yu},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219658},
url = {https://www.mdpi.com/1422-0067/27/21/9658},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 2B9-Fc Ameliorates Immune Thrombocytopenia by Suppressing STAT1-Mediated M1 Macrophage Polarization and Expanding Regulatory T Cells
AU - Shuran Yang
AU - Shuang Xing
AU - Xing Shen
AU - Wanlu Zhu
AU - Mengting Ge
AU - He Xiao
AU - Kaikai Yu
AU - Zuyin Yu
PY - 2026
DA - 2026/10/28
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219658
UR - https://www.mdpi.com/1422-0067/27/21/9658
AB - Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder in which enhanced platelet destruction and impaired platelet production coexist, and a substantial proportion of patients remain refractory to available therapies. Here, we evaluated 2B9-Fc, a thrombopoietin (TPO) mimetic peptide engineered from a cyclic peptide with high affinity for both human and mouse c-MPL, in passive (anti-CD41 monoclonal antibody R300) and active (guinea pig anti-mouse platelet serum, GP-APS) immunization male C57BL/6J and humanized c-MPL receptor transgenic mouse models of ITP. 2B9-Fc (500 μg/kg, subcutaneously) significantly elevated peripheral platelet counts in both models (p < 0.01), without affecting WBC, RBC, or hemoglobin, and alleviated skin purpura and bleeding scores in the active model. In addition, 2B9-Fc treatment was associated with a reduced splenic M1/M2 macrophage ratio, increased regulatory T cells (Tregs), downregulated IL-6 and iNOS while upregulating TGF-β1 and Foxp3, and suppressed STAT1 phosphorylation. In humanized c-MPL receptor transgenic (MT) mice, 2B9-Fc promoted CD41+ megakaryocyte generation in vitro and sustained platelet recovery in vivo through day 14. These results indicate that 2B9-Fc ameliorates ITP and is associated with promotion of megakaryocyte maturation and restoration of immune tolerance, likely involving inhibition of STAT1-mediated M1 polarization and Treg expansion, supporting its potential for clinical translation.
SN - 1422-0067
ER -