Dynamic immune cell profiling identified natural killer cell shift as the key event in early allograft dysfunction after liver transplantation
© 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd..
Early allograft dysfunction (EAD) is a life-threatening and fast-developing complication after liver transplantation. The underlying mechanism needs to be better understood, and there has yet to be an efficient therapeutic target. This study retrospectively reviewed 109 patients undergoing liver transplantation, with dynamic profiling of CD3/4/8/16/19/45/56 on the peripheral immune cells (before transplant and 2-4 days after). Altogether, 35 out of the 109 patients developed EAD after liver transplantation. We observed a significant decrease in the natural killer cell proportion (NK cell shift, p = 0.008). The NK cell shift was linearly correlated with cold ischemic time (p = 0.016) and was potentially related to the recipients' outcomes. In mouse models, ischemic/reperfusion (I/R) treatments induced the recruitment of NK cells from peripheral blood into liver tissues. NK cell depletion blocked a series of immune cascades (including CD8+ CD127+ T cells) and inhibited hepatocyte injury effectively in I/R and liver transplantation models. We further found that I/R treatment increased hepatic expression of the ligands for natural killer group 2 member D (NKG2D), a primary activating cell surface receptor in NK cells. Blockade of NKG2D showed a similar protective effect against I/R injury, indicating its role in NK cell activation and the subsequent immunological injury. Our findings built a bridge for the translation from innate immune response to EAD at the bedside. Peripheral NK cell shift is associated with the incidence of EAD after liver transplantation. NKG2D-mediated NK cell activation is a potential therapeutic target.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:57 |
|---|---|
| Enthalten in: |
Cell proliferation - 57(2024), 4 vom: 30. Apr., Seite e13568 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Lu, Di [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Completed 03.04.2024 Date Revised 03.04.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1111/cpr.13568 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM363975632 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM363975632 | ||
| 003 | DE-627 | ||
| 005 | 20240403235014.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1111/cpr.13568 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1363.xml |
| 035 | |a (DE-627)NLM363975632 | ||
| 035 | |a (NLM)37905596 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Lu, Di |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Dynamic immune cell profiling identified natural killer cell shift as the key event in early allograft dysfunction after liver transplantation |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 03.04.2024 | ||
| 500 | |a Date Revised 03.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd. | ||
| 520 | |a Early allograft dysfunction (EAD) is a life-threatening and fast-developing complication after liver transplantation. The underlying mechanism needs to be better understood, and there has yet to be an efficient therapeutic target. This study retrospectively reviewed 109 patients undergoing liver transplantation, with dynamic profiling of CD3/4/8/16/19/45/56 on the peripheral immune cells (before transplant and 2-4 days after). Altogether, 35 out of the 109 patients developed EAD after liver transplantation. We observed a significant decrease in the natural killer cell proportion (NK cell shift, p = 0.008). The NK cell shift was linearly correlated with cold ischemic time (p = 0.016) and was potentially related to the recipients' outcomes. In mouse models, ischemic/reperfusion (I/R) treatments induced the recruitment of NK cells from peripheral blood into liver tissues. NK cell depletion blocked a series of immune cascades (including CD8+ CD127+ T cells) and inhibited hepatocyte injury effectively in I/R and liver transplantation models. We further found that I/R treatment increased hepatic expression of the ligands for natural killer group 2 member D (NKG2D), a primary activating cell surface receptor in NK cells. Blockade of NKG2D showed a similar protective effect against I/R injury, indicating its role in NK cell activation and the subsequent immunological injury. Our findings built a bridge for the translation from innate immune response to EAD at the bedside. Peripheral NK cell shift is associated with the incidence of EAD after liver transplantation. NKG2D-mediated NK cell activation is a potential therapeutic target | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a NK Cell Lectin-Like Receptor Subfamily K |2 NLM | |
| 700 | 1 | |a Yang, Xinyu |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Linhui |e verfasserin |4 aut | |
| 700 | 1 | |a Lian, Zhengxing |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Winyen |e verfasserin |4 aut | |
| 700 | 1 | |a Zhuo, Jianyong |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Modan |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Zuyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Shusen |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Xiao |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cell proliferation |d 1993 |g 57(2024), 4 vom: 30. Apr., Seite e13568 |w (DE-627)NLM013150766 |x 1365-2184 |7 nnns |
| 773 | 1 | 8 | |g volume:57 |g year:2024 |g number:4 |g day:30 |g month:04 |g pages:e13568 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1111/cpr.13568 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 57 |j 2024 |e 4 |b 30 |c 04 |h e13568 | ||