Open AccessInterleukin‐33 prolongs allograft survival during chronic cardiac rejection
Author(s) -
Brunner Stefan M.,
Schiechl Gabriela,
Falk Werner,
Schlitt Hans J.,
Geissler Edward K.,
FichtnerFeigl Stefan
Publication year - 2011
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/j.1432-2277.2011.01306.x
Subject(s) - medicine , foxp3 , immunology , flow cytometry , cd19 , immune system , proinflammatory cytokine , interleukin 10 , cytokine , interleukin , integrin alpha m , myeloid derived suppressor cell , inflammation , suppressor , cancer
Summary 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.