Chenghao Li, Xing Chen, Yixuan Wang, Yajun Huang, Guohua Wang
Journal of cardiovascular pharmacology 2023 Mar 01Despite advancements in immunosuppressive therapy, acute allograft rejection remains an important challenge for heart transplantation patients. Nuclear factor of activated T-cells 5 (NFAT5), a member of the family of Rel homology domain-containing factors that plays an important role in regulating immune responses of T lymphocytes, may be closely associated with cardiac rejection. KRN2, as a specific inhibitor of NFAT5, is injected intraperitoneally daily starting from day 0 after murine heart transplantation. When compared with saline treatment, KRN2 treatment can improve allograft survival. Histologic examination revealed that the KRN2 treatment group experienced less-severe rejection, and enzyme-linked immunosorbent assay revealed lower levels of inflammatory cytokines in circulating serum. The proportion and number of T-cell subpopulations in the spleens were analyzed by flow cytometry. We found that KRN2 treatment reduced the proportions of CD4 + IFN-γ + , CD4 + IL-17A + , and CD4 + IL-4 + Th cells, whereas increasing CD4 + Foxp3 + Treg cells compared with the control group. These findings suggest that KRN2 attenuates acute allograft rejection by regulating CD4 + T lymphocyte responses. NFAT5 could be a promising therapeutic target for preventing acute allograft rejection. Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.
Chenghao Li, Xing Chen, Yixuan Wang, Yajun Huang, Guohua Wang. Inhibiting NFAT5 With KRN2 Mitigates Acute Allograft Rejection in a Murine Heart Transplantation Model. Journal of cardiovascular pharmacology. 2023 Mar 01;81(3):212-220
PMID: 36651978
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