IL-33 Prolongs Murine Cardiac Allograft Survival Through... : Transplantation (original) (raw)

Basic and Experimental Research

IL-33 Prolongs Murine Cardiac Allograft Survival Through Induction of TH2-Type Immune Deviation

Yin, Hui1,2; Li, Xiang-Yong3; Jin, Xiao-Bao2; Zhang, Bo-Bin1,2; Gong, Quan4; Yang, Heng4; Zheng, Fang4; Gong, Fei-Li4; Zhu, Jia-Yong2,5

1 Department of Microbiology and Immunology, Guangdong Pharmaceutical University, Guangzhou, China.

2 Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, China.

3 Department of Biochemistry and Molecular Biology, Guangdong Medical college, Zhanjiang, China.

4 Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

This work was supported by Medical and Scientific Research Foundation of Guangdong Province (A2008314) and National Development Program (973) for Key Basic Research (2007CB512402) of China.

The authors declare no conflict of interest.

5 Address correspondence to: Jia-yong Zhu, M.D., Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, 280 Waihuandonglu, Guangzhou daxuecheng, Guangzhou 510006, China.

E-mail: [email protected]

Fei-li Gong and Jia-yong Zhu participated in research design; Hui Yin participated in the writing of the manuscript; Xiang-yong Li, Xiao-bao Jin, Bo-bin Zhang, and Quan Gong participated in the performance of the research; and Heng Yang and Fang Zheng participated in data analysis.

Received 8 January 2010. Revision requested 8 January 2010.

Accepted 21 January 2010.

Abstract

Background.

In Th (T helper) 1/Th2 balance in response to signals given during donor antigen presentation, induction of allograft prolongation is more often related to Th2-type than with Th1-type immunity. Here, we examined the effect of interleukin (IL)-33, a novel member of the IL-1 family, on cardiac allograft survival in mice.

Methods.

Mice heterotopic cardiac transplants were performed with sequential recipient sacrifice at anticipated time points to examine the immunoregulatory action of IL-33 in recipient mice.

Results.

In vitro Th1-polarized CD4+ T cells did not express ST2L; however, most CD4+ T cells became ST2L+ on repeated stimulation under Th2-polarizing conditions. Similarly, we found that IL-33 was able to enhance the expression of Th2-associated cytokines (IL-5 and IL-13) but not interferon (IFN)-γ. Treatment of recipient mice with IL-33 results in the improvement of allograft survival (more than 20 days) when compared with phosphate-buffered saline- or glutathione S-transferase-treated groups (all less than 9 days). Intracellular cytokine staining in CD4+ splenocytes confirmed an increase in the percentage of IL-4+ cells and a decrease in the percentage of IFN-γ+ cells in IL-33 treated mice. In addition, IL-33 significantly enhanced the gene expression of Th2-type cytokines IL-4 and IL-5 but suppressed the Th1-type cytokine IFN-γ mRNA levels in both allograft and recipient spleen.

Conclusion.

These data demonstrate that IL-33 serves as a potent inducer of Th2 immune response and can markedly contribute to the prolongation of cardiac allograft survival.