Interleukin 21 (IL-21) regulates chronic allograft vasculopathy (CAV) in murine heart allograft rejection.
| dc.contributor.author | Khattar, Mithun | |
| dc.contributor.author | Baum, Caitlin E | |
| dc.contributor.author | Schroder, Paul | |
| dc.contributor.author | Breidenbach, Joshua D | |
| dc.contributor.author | Haller, Steven T | |
| dc.contributor.author | Chen, Wenhao | |
| dc.contributor.author | Stepkowski, Stanislaw | |
| dc.date.accessioned | 2020-07-07T04:29:34Z | |
| dc.date.available | 2020-07-07T04:29:34Z | |
| dc.date.issued | 2019-01 | |
| dc.date.updated | 2020-07-07T04:29:32Z | |
| dc.description.abstract | IL-21 is the most recently discovered common gamma-chain cytokine that promotes persistent T-cell responses in chronic infections, autoimmunity and cancer. However, the therapeutic potential of inhibiting the IL-21-BATF signaling axis, particularly in transplant rejection, remains unclear. We used heart transplant models to examine the effects of IL-21 blockade in prevention of chronic cardiac allograft vasculopathy (CAV) using genetic knock-out and therapeutic approaches. Both wild-type C57BL/6 and IL-21-/- strains acutely rejected Balb/c skin grafts and once immunized with this skin graft, rejected Balb/c heart allografts in an accelerated fashion. However, when transplanted with heart grafts from the class-II major histocompatibility complex mutant, B6bm12 mice; wild-type recipients developed CAV, while IL-21-/- recipients were protected, even at day 100 post-transplant. Similarly, BATF-/- recipients, lacking the transcription factor BATF responsible for IL-21 production, did not develop CAV in B6-bm12 heart allografts. Strikingly, in a transient treatment protocol, the development of CAV in wild-type recipients of B6-bm12 hearts allografts was blocked by the administration of IL-21 receptor fusion protein (R-Fc). Thus, we demonstrate that CAV is regulated at least in part by IL-21 signaling and its blockade by genetic approaches or therapy with IL-21R-Fc prevents CAV in mice. | |
| dc.identifier | PONE-D-19-18782 | |
| dc.identifier.issn | 1932-6203 | |
| dc.identifier.issn | 1932-6203 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | Public Library of Science (PLoS) | |
| dc.relation.ispartof | PloS one | |
| dc.relation.isversionof | 10.1371/journal.pone.0225624 | |
| dc.subject | T-Lymphocytes | |
| dc.subject | Animals | |
| dc.subject | Mice, Inbred BALB C | |
| dc.subject | Mice, Inbred C57BL | |
| dc.subject | Mice, Knockout | |
| dc.subject | Mice | |
| dc.subject | Vascular Diseases | |
| dc.subject | Recombinant Fusion Proteins | |
| dc.subject | Interleukins | |
| dc.subject | Histocompatibility Antigens Class II | |
| dc.subject | Heart Transplantation | |
| dc.subject | Skin Transplantation | |
| dc.subject | Transplantation, Homologous | |
| dc.subject | Graft Rejection | |
| dc.subject | Basic-Leucine Zipper Transcription Factors | |
| dc.subject | Receptors, Interleukin-21 | |
| dc.subject | Interferon-gamma | |
| dc.title | Interleukin 21 (IL-21) regulates chronic allograft vasculopathy (CAV) in murine heart allograft rejection. | |
| dc.type | Journal article | |
| pubs.begin-page | e0225624 | |
| pubs.issue | 11 | |
| pubs.organisational-group | Staff | |
| pubs.organisational-group | Surgery | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | Clinical Science Departments | |
| pubs.organisational-group | School of Medicine | |
| pubs.publication-status | Published | |
| pubs.volume | 14 |
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