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<p>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.</p>

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Single-cell analysis indicating CCR8 modulates CD8+ tissue-resident memory T cells to attenuates rejection in transplantation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月16日

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  • Xueteng Wang,
  • Xinqiang Li,
  • Hailun Cai,
  • Zhuoyu Jia,
  • Xin Zhou,
  • Ruidong Ding,
  • Meiying Song,
  • Huan Liu,
  • Feng Wang,
  • Bin Wu,
  • Kai Zhao,
  • Shipeng Li,
  • Bei Zhang,
  • Dahong Teng,
  • Jinzhen Cai

摘要

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.