Blocking CCL8-CCR8-Mediated Early Allograft Inflammation Improves Kidney Transplant Function
Copyright © 2022 by the American Society of Nephrology..
BACKGROUND: In kidney transplantation, early allograft inflammation impairs long-term allograft function. However, precise mediators of early kidney allograft inflammation are unclear, making it challenging to design therapeutic interventions.
METHODS: We used an allogeneic murine kidney transplant model in which CD45.2 BALB/c kidneys were transplanted to CD45.1 C57BL/6 recipients.
RESULTS: Donor kidney resident macrophages within the allograft expanded rapidly in the first 3 days. During this period, they were also induced to express a high level of Ccl8, which, in turn, promoted recipient monocyte graft infiltration, their differentiation to resident macrophages, and subsequent expression of Ccl8. Enhanced graft infiltration of recipient CCR8+ T cells followed, including CD4, CD8, and γδ T cells. Consequently, blocking CCL8-CCR8 or depleting donor kidney resident macrophages significantly inhibits early allograft immune cell infiltration and promotes superior short-term allograft function.
CONCLUSIONS: Targeting the CCL8-CCR8 axis is a promising measure to reduce early kidney allograft inflammation.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:33 |
|---|---|
| Enthalten in: |
Journal of the American Society of Nephrology : JASN - 33(2022), 10 vom: 16. Okt., Seite 1876-1890 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Dangi, Anil [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 13.01.2023 Date Revised 02.10.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1681/ASN.2022020139 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM344923886 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM344923886 | ||
| 003 | DE-627 | ||
| 005 | 20231226023904.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1681/ASN.2022020139 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1149.xml |
| 035 | |a (DE-627)NLM344923886 | ||
| 035 | |a (NLM)35973731 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Dangi, Anil |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Blocking CCL8-CCR8-Mediated Early Allograft Inflammation Improves Kidney Transplant Function |
| 264 | 1 | |c 2022 | |
| 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 13.01.2023 | ||
| 500 | |a Date Revised 02.10.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 by the American Society of Nephrology. | ||
| 520 | |a BACKGROUND: In kidney transplantation, early allograft inflammation impairs long-term allograft function. However, precise mediators of early kidney allograft inflammation are unclear, making it challenging to design therapeutic interventions | ||
| 520 | |a METHODS: We used an allogeneic murine kidney transplant model in which CD45.2 BALB/c kidneys were transplanted to CD45.1 C57BL/6 recipients | ||
| 520 | |a RESULTS: Donor kidney resident macrophages within the allograft expanded rapidly in the first 3 days. During this period, they were also induced to express a high level of Ccl8, which, in turn, promoted recipient monocyte graft infiltration, their differentiation to resident macrophages, and subsequent expression of Ccl8. Enhanced graft infiltration of recipient CCR8+ T cells followed, including CD4, CD8, and γδ T cells. Consequently, blocking CCL8-CCR8 or depleting donor kidney resident macrophages significantly inhibits early allograft immune cell infiltration and promotes superior short-term allograft function | ||
| 520 | |a CONCLUSIONS: Targeting the CCL8-CCR8 axis is a promising measure to reduce early kidney allograft inflammation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a acute allograft rejection | |
| 650 | 4 | |a allografts | |
| 650 | 4 | |a inflammation | |
| 650 | 4 | |a kidney transplantation | |
| 650 | 4 | |a macrophages | |
| 650 | 7 | |a Ccr8 protein, mouse |2 NLM | |
| 650 | 7 | |a Receptors, CCR8 |2 NLM | |
| 700 | 1 | |a Husain, Irma |e verfasserin |4 aut | |
| 700 | 1 | |a Jordan, Collin Z |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Shuangjin |e verfasserin |4 aut | |
| 700 | 1 | |a Natesh, Naveen |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Xiling |e verfasserin |4 aut | |
| 700 | 1 | |a Kwun, Jean |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Xunrong |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of the American Society of Nephrology : JASN |d 1990 |g 33(2022), 10 vom: 16. Okt., Seite 1876-1890 |w (DE-627)NLM012606502 |x 1533-3450 |7 nnns |
| 773 | 1 | 8 | |g volume:33 |g year:2022 |g number:10 |g day:16 |g month:10 |g pages:1876-1890 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1681/ASN.2022020139 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 33 |j 2022 |e 10 |b 16 |c 10 |h 1876-1890 | ||