Balam, Saidou and Schiechl-Brachner, Gabriela and Buchtler, Simone and Halbritter, Dagmar and Schmidbauer, Kathrin and Talke, Yvonne and Neumayer, Sophia and Salewski, Jan-Niklas and Winter, Frederike and Karasuyama, Hajime and Yamanishi, Yoshinori and Renner, Kerstin and Geissler, Edward K. and Mack, Matthias (2019) IL-3 Triggers Chronic Rejection of Cardiac Allografts by Activation of Infiltrating Basophils. JOURNAL OF IMMUNOLOGY, 202 (12). pp. 3514-3523. ISSN 0022-1767, 1550-6606
Full text not available from this repository. (Request a copy)Abstract
Chronic rejection is a major problem in transplantation medicine, largely resistant to therapy, and poorly understood. We have shown previously that basophil-derived IL-4 contributes to fibrosis and vasculopathy in a model of heart transplantation with depletion of CD4(+) T cells. However, it is unknown how basophils are activated in the allografts and whether they play a role when cyclosporin A (CsA) immunosuppression is applied. BALB/c donor hearts were heterotopically transplanted into fully MHC-mismatched C57BL/6 recipients and acute rejection was prevented by depletion of CD4(+) T cells or treatment with CsA. We found that IL-3 is significantly upregulated in chronically rejecting allografts and is the major activator of basophils in allografts. Using IL-3-deficient mice and depletion of basophils, we show that IL-3 contributes to allograft fibrosis and organ failure in a basophil-dependent manner. Also, in the model of chronic rejection involving CsA, IL-3 and basophils substantially contribute to organ remodeling, despite the almost complete suppression of IL-4 by CsA. In this study, basophil-derived IL-6 that is resistant to suppression by CsA, was largely responsible for allograft fibrosis and limited transplant survival. Our data show that IL-3 induces allograft fibrosis and chronic rejection of heart transplants, and exerts its profibrotic effects by activation of infiltrating basophils. Blockade of IL-3 or basophil-derived cytokines may provide new strategies to prevent or delay the development of chronic allograft rejection.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GROWTH-FACTOR-BETA; DIFFERENTIAL REGULATION; BLOOD BASOPHILS; TISSUE-REPAIR; T-CELLS; INTERLEUKIN-3; FIBROSIS; IMMUNITY; HEART; TRANSPLANTATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Apr 2020 08:11 |
| Last Modified: | 08 Apr 2020 08:11 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26831 |
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