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Review
. 2025 Apr 11:16:1544960.
doi: 10.3389/fimmu.2025.1544960. eCollection 2025.

Triple role of exosomes in lung transplantation

Dingyu Rao  1 , Defa Huang  2 , Zongbo Peng  3 , Dewang Xiao  3 , Chunfa Xie  1 , Shenyu Zhu  1 , Haoquan He  4 , Zhixian Tang  1 , Zhongkai Wu  5 , Zuxiong Zhang  1
Affiliations
Review

Triple role of exosomes in lung transplantation

Dingyu Rao et al. Front Immunol. .

Abstract

Exosomes are tiny vesicles secreted by the vast majority of cells and play an important role in physiological as well as pathological processes in the body. Circulating exosomes in Lung Transplant Recipients (LTxR) undergoing rejection contain mismatched Human Leukocyte Antigens (HLA) and lung-associated autoantigens (e.g., K-alpha1 microtubule protein and collagen V), which may induce autoantibodies, and the circulating exosomes trigger an immune response that results in rejection of the lung transplant recipient. This article discusses the role of exosomes in lung transplantation from three perspectives: exosomes as a biomarker for rejection after lung transplantation; the mechanism of exosome-mediated activation of the immune response; and the potential of exosomes as a therapeutic strategy.

Keywords: DCs; allograft immunization; biomark assay; exosome; lung transplantation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Three roles of the exosomes in transplantation recipients or in transplantation models: (A) Role as Antigen-Presenting Vesicles; (B) Role as as biomarkers; (C) Role as therapeutic strategies.
Figure 2
Figure 2
Exosome mediated allogeneic recognition of T cells in local lymph nodes: (A) Exosomes released from allogeneic grafts or donor DCs are captured by recipient DCs and their cognate MHC is expressed on the surface of the recipient DCs (called cross-modified cells). The cross-modified cells present the cognate MHC peptide to T cells; (B) In addition to APC, exosomes secreted by allogeneic grafts or donor DCs can directly present their allo-MHC-peptides to T cells.
Figure 3
Figure 3
Two ways of DC derived exosomes (DC-EXO) mediated antigen presentation. (1) DC-EXO can directly present antigen to T cells and stimulate T cell activation; (2) After binding to APCs, DC-EXO merges with the acceptor APC surface membrane and transfers its peptide/MHC complexes. Following internalization, the DC-EXO peptide/MHC complexes can be reprocessed via endosomal pathways within the APC. Peptide complexes can then be transported back to the DC’s surface for presentation to T cells.
Figure 4
Figure 4
Therapeutic Strategies for Exosomes in LTx Rejection. (A) Exosomes have high membrane penetrability, making them excellent drug carriers; (B) Exosomes can regulate Epithelial-Mesenchymal Transition (EMT) markers expression in bronchial epithelial cells; (C) Exosomes can improve injured bronchial endothelium.
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