Interleukin 21 (IL-21) regulates chronic allograft vasculopathy (CAV) in murine heart allograft rejection.
Animals
Basic-Leucine Zipper Transcription Factors
/ deficiency
Graft Rejection
/ etiology
Heart Transplantation
/ adverse effects
Histocompatibility Antigens Class II
/ genetics
Interferon-gamma
/ metabolism
Interleukins
/ deficiency
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Receptors, Interleukin-21
/ genetics
Recombinant Fusion Proteins
/ administration & dosage
Skin Transplantation
/ adverse effects
T-Lymphocytes
/ cytology
Transplantation, Homologous
/ adverse effects
Vascular Diseases
/ etiology
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
03
07
2019
accepted:
09
11
2019
entrez:
23
11
2019
pubmed:
23
11
2019
medline:
21
3
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31756235
doi: 10.1371/journal.pone.0225624
pii: PONE-D-19-18782
pmc: PMC6874341
doi:
Substances chimiques
Basic-Leucine Zipper Transcription Factors
0
Batf protein, mouse
0
Histocompatibility Antigens Class II
0
Interleukins
0
Receptors, Interleukin-21
0
Recombinant Fusion Proteins
0
Interferon-gamma
82115-62-6
interleukin-21
MKM3CA6LT1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0225624Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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