Interleukin‐2/anti‐interleukin‐2 immune complex attenuates cold ischemia‐reperfusion injury after kidney transplantation by increasing renal regulatory T cells
Abstract Background Cold ischemia‐reperfusion injury (IRI) is an unavoidable complication of kidney transplantation. We investigated the role of regulatory T cells (Treg) in cold IRI and whether the interleukin (IL)‐2/anti‐IL‐2 antibody complex (IL‐2C) can ameliorate cold IRI. Methods We developed a...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-03-01
|
| Series: | Clinical and Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/ctm2.1631 |
| _version_ | 1827307679312248832 |
|---|---|
| author | Joon Young Jang Hyung Woo Kim Ji‐Jing Yan Tae Kyeom Kang Wook‐Bin Lee Beom Seok Kim Jaeseok Yang |
| author_facet | Joon Young Jang Hyung Woo Kim Ji‐Jing Yan Tae Kyeom Kang Wook‐Bin Lee Beom Seok Kim Jaeseok Yang |
| author_sort | Joon Young Jang |
| collection | DOAJ |
| description | Abstract Background Cold ischemia‐reperfusion injury (IRI) is an unavoidable complication of kidney transplantation. We investigated the role of regulatory T cells (Treg) in cold IRI and whether the interleukin (IL)‐2/anti‐IL‐2 antibody complex (IL‐2C) can ameliorate cold IRI. Methods We developed a cold IRI mouse model using kidney transplantation and analyzed the IL‐2C impact on cold IRI in acute, subacute and chronic phases. Results Treg transfer attenuated cold IRI, while Treg depletion aggravated cold IRI. Next, IL‐2C administration prior to IRI mitigated acute renal function decline, renal tissue damage and apoptosis and inhibited infiltration of effector cells into kidneys and pro‐inflammatory cytokine expression on day 1 after IRI. On day 7 after IRI, IL‐2C promoted renal regeneration and reduced subacute renal damage. Furthermore, on day 28 following IRI, IL‐2C inhibited chronic fibrosis. IL‐2C decreased reactive oxygen species‐mediated injury and improved antioxidant function. When IL‐2C was administered following IRI, it also increased renal regeneration with Treg infiltration and suppressed renal fibrosis. In contrast, Treg depletion in the presence of IL‐2C eliminated the positive effects of IL‐2C on IRI. Conclusion Tregs protect kidneys from cold IRI and IL‐2C inhibited cold IRI by increasing the renal Tregs, suggesting a potential of IL‐2C in treating cold IRI. Key Points Interleukin (IL)‐2/anti‐IL‐2 antibody complex attenuated acute renal injury, facilitated subacute renal regeneration and suppressed chronic renal fibrosis after cold ischemia‐reperfusion injury (IRI) by increasing the renal Tregs. IL‐2/anti‐IL‐2 antibody complex decreased reactive oxygen species‐mediated injury and improved antioxidant function. This study suggests the therapeutic potential of the IL‐2/anti‐IL‐2 antibody complex in kidney transplantation‐associated cold IR. |
| first_indexed | 2024-04-24T18:43:39Z |
| format | Article |
| id | doaj.art-e9e6609437e44f5fb43a7ce1221eba72 |
| institution | Directory Open Access Journal |
| issn | 2001-1326 |
| language | English |
| last_indexed | 2024-04-24T18:43:39Z |
| publishDate | 2024-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Medicine |
| spelling | doaj.art-e9e6609437e44f5fb43a7ce1221eba722024-03-27T09:22:32ZengWileyClinical and Translational Medicine2001-13262024-03-01143n/an/a10.1002/ctm2.1631Interleukin‐2/anti‐interleukin‐2 immune complex attenuates cold ischemia‐reperfusion injury after kidney transplantation by increasing renal regulatory T cellsJoon Young Jang0Hyung Woo Kim1Ji‐Jing Yan2Tae Kyeom Kang3Wook‐Bin Lee4Beom Seok Kim5Jaeseok Yang6Department of Internal Medicine Yonsei University College of Medicine Seoul Republic of KoreaDepartment of Internal Medicine Yonsei University College of Medicine Seoul Republic of KoreaDepartment of Internal Medicine Yonsei University College of Medicine Seoul Republic of KoreaNatural Product Research Center Korea Institute of Science and Technology Gangneung Republic of KoreaNatural Product Research Center Korea Institute of Science and Technology Gangneung Republic of KoreaDepartment of Internal Medicine Yonsei University College of Medicine Seoul Republic of KoreaDepartment of Internal Medicine Yonsei University College of Medicine Seoul Republic of KoreaAbstract Background Cold ischemia‐reperfusion injury (IRI) is an unavoidable complication of kidney transplantation. We investigated the role of regulatory T cells (Treg) in cold IRI and whether the interleukin (IL)‐2/anti‐IL‐2 antibody complex (IL‐2C) can ameliorate cold IRI. Methods We developed a cold IRI mouse model using kidney transplantation and analyzed the IL‐2C impact on cold IRI in acute, subacute and chronic phases. Results Treg transfer attenuated cold IRI, while Treg depletion aggravated cold IRI. Next, IL‐2C administration prior to IRI mitigated acute renal function decline, renal tissue damage and apoptosis and inhibited infiltration of effector cells into kidneys and pro‐inflammatory cytokine expression on day 1 after IRI. On day 7 after IRI, IL‐2C promoted renal regeneration and reduced subacute renal damage. Furthermore, on day 28 following IRI, IL‐2C inhibited chronic fibrosis. IL‐2C decreased reactive oxygen species‐mediated injury and improved antioxidant function. When IL‐2C was administered following IRI, it also increased renal regeneration with Treg infiltration and suppressed renal fibrosis. In contrast, Treg depletion in the presence of IL‐2C eliminated the positive effects of IL‐2C on IRI. Conclusion Tregs protect kidneys from cold IRI and IL‐2C inhibited cold IRI by increasing the renal Tregs, suggesting a potential of IL‐2C in treating cold IRI. Key Points Interleukin (IL)‐2/anti‐IL‐2 antibody complex attenuated acute renal injury, facilitated subacute renal regeneration and suppressed chronic renal fibrosis after cold ischemia‐reperfusion injury (IRI) by increasing the renal Tregs. IL‐2/anti‐IL‐2 antibody complex decreased reactive oxygen species‐mediated injury and improved antioxidant function. This study suggests the therapeutic potential of the IL‐2/anti‐IL‐2 antibody complex in kidney transplantation‐associated cold IR.https://doi.org/10.1002/ctm2.1631cold ischemia‐reperfusion injuryIL‐2/anti‐IL‐2 immune complexkidney transplantationregulatory T cells |
| spellingShingle | Joon Young Jang Hyung Woo Kim Ji‐Jing Yan Tae Kyeom Kang Wook‐Bin Lee Beom Seok Kim Jaeseok Yang Interleukin‐2/anti‐interleukin‐2 immune complex attenuates cold ischemia‐reperfusion injury after kidney transplantation by increasing renal regulatory T cells Clinical and Translational Medicine cold ischemia‐reperfusion injury IL‐2/anti‐IL‐2 immune complex kidney transplantation regulatory T cells |
| title | Interleukin‐2/anti‐interleukin‐2 immune complex attenuates cold ischemia‐reperfusion injury after kidney transplantation by increasing renal regulatory T cells |
| title_full | Interleukin‐2/anti‐interleukin‐2 immune complex attenuates cold ischemia‐reperfusion injury after kidney transplantation by increasing renal regulatory T cells |
| title_fullStr | Interleukin‐2/anti‐interleukin‐2 immune complex attenuates cold ischemia‐reperfusion injury after kidney transplantation by increasing renal regulatory T cells |
| title_full_unstemmed | Interleukin‐2/anti‐interleukin‐2 immune complex attenuates cold ischemia‐reperfusion injury after kidney transplantation by increasing renal regulatory T cells |
| title_short | Interleukin‐2/anti‐interleukin‐2 immune complex attenuates cold ischemia‐reperfusion injury after kidney transplantation by increasing renal regulatory T cells |
| title_sort | interleukin 2 anti interleukin 2 immune complex attenuates cold ischemia reperfusion injury after kidney transplantation by increasing renal regulatory t cells |
| topic | cold ischemia‐reperfusion injury IL‐2/anti‐IL‐2 immune complex kidney transplantation regulatory T cells |
| url | https://doi.org/10.1002/ctm2.1631 |
| work_keys_str_mv | AT joonyoungjang interleukin2antiinterleukin2immunecomplexattenuatescoldischemiareperfusioninjuryafterkidneytransplantationbyincreasingrenalregulatorytcells AT hyungwookim interleukin2antiinterleukin2immunecomplexattenuatescoldischemiareperfusioninjuryafterkidneytransplantationbyincreasingrenalregulatorytcells AT jijingyan interleukin2antiinterleukin2immunecomplexattenuatescoldischemiareperfusioninjuryafterkidneytransplantationbyincreasingrenalregulatorytcells AT taekyeomkang interleukin2antiinterleukin2immunecomplexattenuatescoldischemiareperfusioninjuryafterkidneytransplantationbyincreasingrenalregulatorytcells AT wookbinlee interleukin2antiinterleukin2immunecomplexattenuatescoldischemiareperfusioninjuryafterkidneytransplantationbyincreasingrenalregulatorytcells AT beomseokkim interleukin2antiinterleukin2immunecomplexattenuatescoldischemiareperfusioninjuryafterkidneytransplantationbyincreasingrenalregulatorytcells AT jaeseokyang interleukin2antiinterleukin2immunecomplexattenuatescoldischemiareperfusioninjuryafterkidneytransplantationbyincreasingrenalregulatorytcells |