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Single-cell analysis indicating CCR8 modulates CD8+ tissue-resident memory T cells to attenuates rejection in transplantation
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Single-cell analysis indicating CCR8 modulates CD8+ tissue-resident memory T cells to attenuates rejection in transplantation
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Journal Article
Single-cell analysis indicating CCR8 modulates CD8+ tissue-resident memory T cells to attenuates rejection in transplantation
2025
Overview
Immune rejection poses a major challenge in organ transplantation, with tissue-resident memory T (TRM) cells playing a critical role in graft rejection. This study investigated the impact of CCR8 on TRM cells using single-cell RNA sequencing (scRNA-seq), flow cytometry, and immunohistochemistry. The results show that CCR8 expression was upregulated on CD8⁺ TRM cells after transplantation, peaking on day 7. Blocking or knocking out CCR8, as well as neutralizing CCL1 and CCL8, significantly reduced CD8⁺ TRM cell accumulation in the graft and their cytokine production. These treatments prolonged graft survival, alleviated rejection severity, and impaired the ability of CD8⁺ TRM cells to produce GZMB, IFN-γ, and IL-2. Single-cell analysis of skin transplantation revealed that loss of CCR8 disrupted macrophage–T cell interactions, particularly CD8⁺ TRM–macrophage crosstalk, while enhancing CD40, PD-L1, and NRG signaling. These findings suggest that targeting CCR8 to limit the accumulation and function of CD8⁺ TRM cells may be an effective strategy to alleviate transplant rejection.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 631/80
/ Animals
/ Blood
/ CCR8
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - metabolism
/ Cells
/ Graft Rejection - immunology
/ Graft Rejection - prevention & control
/ Humanities and Social Sciences
/ Ligands
/ Male
/ Mice
/ Proteins
/ Receptors, CCR8 - immunology
/ Receptors, CCR8 - metabolism
/ Science
/ Single-Cell Analysis - methods
/ Software
/ Sutures
