Interleukin-33 prolongs allograft survival during chronic cardiac rejection

Brunner, Stefan M. and Schiechl, Gabriela and Falk, Werner and Schlitt, Hans J. and Geissler, Edward K. and Fichtner-Feigl, Stefan (2011) Interleukin-33 prolongs allograft survival during chronic cardiac rejection. TRANSPLANT INTERNATIONAL, 24 (10). pp. 1027-1039. ISSN 0934-0874,

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Abstract

Interleukin-33 (IL-33) stimulates the generation of cells and cytokines characteristic of a Th2 immune response. We examined the effects of IL-33 on allografted heart tissue in a chronic cardiac rejection model, including analysis of the peripheral myeloid and lymphoid compartments. B6. C-H2bm12/KhEg hearts were transplanted into MHC class II-mismatched C57Bl/6J mice; IL-33 was administered daily. Cells from allografts and spleens were isolated for flow cytometry and cultured for cytokine production; some tissues were used for immunohistochemistry. Animals treated with IL-33 showed significantly longer allograft survival, which was associated with a distinct cytokine profile produced by graft-infiltrating cells. Proinflammatory IL-17A production was decreased with IL-33 treatment, while increased levels of IL-5, IL-10, and IL-13 were observed. After IL-33 therapy, flow cytometry showed a direct induction of CD4(+) Foxp3(+) Treg, whereas the number of B220(+) CD19(+) B cells, and circulating, as well as allograft deposited, alloantibodies was reduced. Following IL-33 treatment, a significant decrease in graft-infiltrating CD11b(high) Gr1(high) granulocytes coincided with a significant increase in CD11b(high) Gr1(intermediate) myeloid-derived suppressor cells (MDSC). In conclusion, IL-33 treatment in the setting of chronic rejection promotes the development of a Th2-type immune response that favors MDSC and Treg expansion, reduces antibody-mediated rejection (AMR), and ultimately, prolongs allograft survival.

Item Type: Article
Uncontrolled Keywords: REGULATORY T-CELLS; TRANSPLANTED MOUSE HEARTS; SUPPRESSOR-CELLS; INTERFERON-GAMMA; AIRWAY INFLAMMATION; HUMAN BASOPHILS; IL-1 FAMILY; MAST-CELLS; GM-CSF; TOLERANCE; allograft survival; antibody-mediated rejection; cardiac transplantation; interleukin-33; myeloid-derived suppressor cells; Treg
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Chirurgie
Medicine > Lehrstuhl für Innere Medizin I
Depositing User: Dr. Gernot Deinzer
Date Deposited: 29 May 2020 10:22
Last Modified: 29 May 2020 10:22
URI: https://pred.uni-regensburg.de/id/eprint/20143

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