IL-34 is a Treg-specific cytokine and mediates transplant tolerance
Cytokines and metabolic pathway-controlling enzymes regulate immune responses and have potential as powerful tools to mediate immune tolerance. Blockade of the interaction between CD40 and CD40L induces long-term cardiac allograft survival in rats through a CD8+CD45RClo Treg potentiation. Here, we have shown that the cytokine IL-34, the immunoregulatory properties of which have not been previously studied in transplantation or T cell biology, is expressed by rodent CD8+CD45RClo Tregs and human FOXP3+CD45RCloCD8+ and CD4+ Tregs. IL-34 was involved in the suppressive function of both CD8+ and CD4+ Tregs and markedly inhibited alloreactive immune responses. Additionally, in a rat cardiac allograft model, IL-34 potently induced transplant tolerance that was associated with a total inhibition of alloantibody production. Treatment of rats with IL-34 promoted allograft tolerance that was mediated by induction of CD8+ and CD4+ Tregs. Moreover, these Tregs were capable of serial tolerance induction through modulation of macrophages that migrate early to the graft. Finally, we demonstrated that human macrophages cultured in the presence of IL-34 greatly expanded CD8+ and CD4+ FOXP3+ Tregs, with a superior suppressive potential of antidonor immune responses compared with non-IL-34-expanded Tregs. In conclusion, we reveal that IL-34 serves as a suppressive Treg-specific cytokine and as a tolerogenic cytokine that efficiently inhibits alloreactive immune responses and mediates transplant tolerance..
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:125 |
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| Enthalten in: |
The journal of clinical investigation - 125(2015), 10, Seite 3952 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bézie, Séverine [VerfasserIn] |
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| Links: |
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| doi: |
10.1172/JCI81227 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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OLC1962309487 |
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| 520 | |a Cytokines and metabolic pathway-controlling enzymes regulate immune responses and have potential as powerful tools to mediate immune tolerance. Blockade of the interaction between CD40 and CD40L induces long-term cardiac allograft survival in rats through a CD8+CD45RClo Treg potentiation. Here, we have shown that the cytokine IL-34, the immunoregulatory properties of which have not been previously studied in transplantation or T cell biology, is expressed by rodent CD8+CD45RClo Tregs and human FOXP3+CD45RCloCD8+ and CD4+ Tregs. IL-34 was involved in the suppressive function of both CD8+ and CD4+ Tregs and markedly inhibited alloreactive immune responses. Additionally, in a rat cardiac allograft model, IL-34 potently induced transplant tolerance that was associated with a total inhibition of alloantibody production. Treatment of rats with IL-34 promoted allograft tolerance that was mediated by induction of CD8+ and CD4+ Tregs. Moreover, these Tregs were capable of serial tolerance induction through modulation of macrophages that migrate early to the graft. Finally, we demonstrated that human macrophages cultured in the presence of IL-34 greatly expanded CD8+ and CD4+ FOXP3+ Tregs, with a superior suppressive potential of antidonor immune responses compared with non-IL-34-expanded Tregs. In conclusion, we reveal that IL-34 serves as a suppressive Treg-specific cytokine and as a tolerogenic cytokine that efficiently inhibits alloreactive immune responses and mediates transplant tolerance. | ||
| 540 | |a Nutzungsrecht: © COPYRIGHT 2015 American Society for Clinical Investigation | ||
| 650 | 4 | |a Interleukins - immunology | |
| 650 | 4 | |a Macrophage Colony-Stimulating Factor - physiology | |
| 650 | 4 | |a Interleukins - biosynthesis | |
| 650 | 4 | |a CD8-Positive T-Lymphocytes - immunology | |
| 650 | 4 | |a RNA, Messenger - biosynthesis | |
| 650 | 4 | |a Recombinant Fusion Proteins - genetics | |
| 650 | 4 | |a T-Lymphocytes, Regulatory - immunology | |
| 650 | 4 | |a Receptor, Macrophage Colony-Stimulating Factor - immunology | |
| 650 | 4 | |a Forkhead Transcription Factors - analysis | |
| 650 | 4 | |a Interleukins - pharmacology | |
| 650 | 4 | |a T-Lymphocyte Subsets - immunology | |
| 650 | 4 | |a Macrophages - drug effects | |
| 650 | 4 | |a Macrophages - immunology | |
| 650 | 4 | |a Dependovirus - genetics | |
| 650 | 4 | |a CD4-Positive T-Lymphocytes - immunology | |
| 650 | 4 | |a Allografts - immunology | |
| 650 | 4 | |a Antigens, CD45 - analysis | |
| 650 | 4 | |a Interleukins - genetics | |
| 650 | 4 | |a Transplantation of organs, tissues, etc | |
| 650 | 4 | |a Health aspects | |
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| 650 | 4 | |a Patient outcomes | |
| 650 | 4 | |a Cytokines | |
| 650 | 4 | |a Research | |
| 650 | 4 | |a Immunological tolerance | |
| 650 | 4 | |a Immunological research | |
| 650 | 4 | |a Transplants & implants | |
| 650 | 4 | |a Animals | |
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| 700 | 1 | |a Ossart, Jason |4 oth | |
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| 700 | 1 | |a Usal, Claire |4 oth | |
| 700 | 1 | |a Renaudin, Karine |4 oth | |
| 700 | 1 | |a Anegon, Ignacio |4 oth | |
| 700 | 1 | |a Guillonneau, Carole |4 oth | |
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| 856 | 4 | 1 | |u http://dx.doi.org/10.1172/JCI81227 |3 Volltext |
| 856 | 4 | 2 | |u http://www.ncbi.nlm.nih.gov/pubmed/26389674 |
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