ORIGINAL RESEARCH article
Front. Immunol.
Sec. Immunological Tolerance and Regulation
Pig regulatory macrophages as a donor-derived immune modulators in xenotransplantation
Provisionally accepted
Chi Phu Vu1
Nhat Minh Dang1Vinh Phuoc Nguyen1Jonghyeok Jung1Joohyun Shim2
Jeong Ho Hwang3
Xoan Hoang Thi4
IK JIN YUN5
Jae Young Kim1*- 1Gachon University, Seongnam, Republic of Korea
- 2Optipharm Co Ltd, Cheongju-si, Republic of Korea
- 3Korea Institute of Toxicology, Daejeon, Republic of Korea
- 4Nguyen Tat Thanh University NTT Hi-Tech Institute, Ho Chi Minh City, Vietnam
- 5Konkuk University School of Medicine, Gwangjin-gu, Republic of Korea
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Xenotransplantation represents a promising strategy to overcome the shortage of donor organs, yet graft survival remains hampered by xeno-immune activation and coagulation dysregulation. Here, we investigated the immunomodulatory properties of pig regulatory macrophages (pMregs) as donor-derived cellular immunotherapy. pMregs were generated from pig CD14⁺ monocytes using M-CSF and IFN-γ and exhibited the canonical Mreg phenotype (CD14⁺CD16⁺CD163⁺PD-L1⁺DHRS9⁺CD32⁻CD169⁻). Functionally, pMregs secreted IL-10 and TGF-β, suppressed the proliferation of not only pig but also monkey and human T cells, and induced FOXP3⁺ Tregs. Importantly, pMregs attenuated inflammatory cytokine production in human M1 macrophages exposed to pig endothelial cells and downregulated the mRNA expression of coagulation-related genes (TF, PAR-1) in this in vitro model. These findings highlight the cross-species immunosuppressive activity and coagulation-regulatory capacity of pMregs, suggesting potential relevance to pathways involved in xenograft injury. pMregs therefore represent a promising candidate for further investigation as a donor-derived immunoregulatory cell type to complement genetically engineered pig grafts.
Keywords: pig regulatory macrophages, xenotransplantation, Inflammation, Immunomodulation, coagulation
Received: 05 Oct 2025; Accepted: 21 Nov 2025.
Copyright: © 2025 Phu Vu, Dang, Nguyen, Jung, Shim, Hwang, Hoang Thi, YUN and Kim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jae Young Kim, jykim85@gachon.ac.kr
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