A pathogenic role of IL- 17 at the early stage of corneal allograft rejection

Chen, Haiyong; Wang, Weilin; Xie, Haiyang; Xu, Xiao; Wu, Jian; Zhao, Jiang; Zhang, Mangli; Zhou, Lin; Zheng, Shusen

doi:10.1016/j.trim.2009.03.006

Cited by 66 publications

(53 citation statements)

References 40 publications

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“…These findings also agree with a recent report that that Th17 cells have a disease-promoting function at the early stage of corneal allograft rejection. 30 Furthermore, in line with our results, it has been shown that in addition to IL-1a, HMGB1 as a second mediator released from damaged human endothelial cells modulates alloreactive T-cell IFN-g and IL-17 production. Interestingly, HMGB1 functions by inducing IL-1b secretion from monocytes through TLR4 and CD14.…”

Section: Discussionsupporting

confidence: 89%

High-mobility group box 1 promotes early acute allograft rejection by enhancing IL-6-dependent Th17 alloreactive response

Duan

Wang

Chen

et al. 2011

Laboratory Investigation

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Previously, we reported that extracellular high-mobility group box 1 (HMGB1) functions as an innate alarmin implicated in cardiac allograft acute rejection. We now present evidence suggesting that HMGB1 is pivotal in inducing interleukin-17 (IL-17)-producing alloreactive T cells by stimulating dendritic cells secretion of IL-6. Those IL-17 þ T cells are likely to be the major effector cells responsible for the early stage of cardiac allograft rejection through mediating an influx of neutrophils into allografts, and therefore, blockade of IL-17A significantly prolonged murine cardiac allograft survival. In contrast to the classical model for a dominant role of IFN-g þ -Th1 cells have in acute allograft rejection, our data suggest that IFN-g þ -Th1 cells are responsible for the late stage of graft destruction by inducing monocyte infiltration when IL-17 þ T-cell response recedes. Blockade of HMGB1 significantly decreased splenic alloreactive Th17 cells and IFN-g-producing CD8 þ T cells in the recipients, leading to less infiltration of neutrophils along with lower IL-6 and IL-17 expression levels in the grafts as well as prolongation of cardiac allograft survival. Together, these data support a novel model in which HMGB1 induces IL-17-producing alloreactive T cells to mediate early stage of allograft rejection, whereas IFN-g-producing alloreactive Th1 cells provoke graft destruction after Th17 response recedes.

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Section: Discussionsupporting

confidence: 89%

High-mobility group box 1 promotes early acute allograft rejection by enhancing IL-6-dependent Th17 alloreactive response

Duan

Wang

Chen

et al. 2011

Laboratory Investigation

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“…36 Finally, using murine graft versus host disease model systems, varied immune responses have been observed between BALB/c and C57BL/6 mice; injection of C57BL/6-splenocytes (H-2 b ) to BDF1 mice or CBF1 mice (H-2 b/d ) results in the development of acute graft versus host disease, whereas injection of DBA/2-or BALB/c-splenocytes (H-2 d ) to BDF1 or CBF1 mice results in chronic graft versus host disease. 37,38 Therefore, phenotypic differences in distinct strain combinations likely explain the disparate role of IL-17 in acute rejection in heart transplants.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-17 Accelerates Allograft Rejection by Suppressing Regulatory T Cell Expansion

et al. 2011

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Background-Interleukin-17 , which is predominantly produced by T helper 17 cells distinct from T helper 1 or T helper 2 cells, participates in the pathogenesis of infectious, autoimmune, and allergic disorders. However, the precise role in allograft rejection remains uncertain. In the present study, we investigated the role of IL-17 in acute allograft rejection using IL-17-deficient mice. Methods and Results-Donor hearts from FVB mice were heterotopically transplanted into either C57BL/6J-IL-17-deficient (IL-17

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“…Study in acute rat renal allograft rejection model has also identified an elevation of IL-17 protein as early as 2 d after transplantation (Hsieh et al, 2001). Th17 expression was markedly increased in inflamed transplants and draining lymph nodes at the early stage of allocorneal rejection in mouse (Chen H. et al, 2009). In a mouse heart transplantation model, antagonism of the IL-17 pathway via administration of an IL-17 inhibitor can reduce intragraft production of inflammatory cytokines and prolong graft survival (Yuan et al, 2008;.…”

Section: Cd4mentioning

confidence: 99%

Th17 promotes acute rejection following liver transplantation in rats

Xie

Zhou

et al. 2010

J. Zhejiang Univ. Sci. B

Self Cite

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T help cell 17 (Th17), recently identified as a new subset of CD4 + T cells, has been implicated in autoimmune diseases, tumor immunity, and transplant rejection. To investigate the role of Th17 in acute hepatic rejection, a rat model of allogeneic liver transplantation (Dark Agouti (DA) to Brown Norway (BN)) was established and isogeneic liver transplantation (BN to BN) was used as controls in the study. The expression of Th17-related cytokines in the liver and peripheral blood was determined by immunohistochemistry, flow cytometry, enzyme-linked immunosorbent assay (ELISA), or real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Strong expression of interleukin-17A (IL-17A), IL-6, transforming growth factor-β (TGF-β), IL-8, and myeloperoxidase (MPO) was observed in liver allografts. The ratios of Th17 to CD4 + lymphocytes in the liver and peripheral blood were dramatically increased in the allograft group compared with the control (P<0.01). Secreted IL-17 and IL-6 in liver homogenate and serum were significantly elevated in the allograft group, while secreted TGF-β was increased in liver homogenate and decreased in serum compared with the control (P<0.01). The messenger RNA (mRNA) levels of IL-17, IL-21, and IL-23 were enhanced in the allografts compared with the control (P<0.01). Correlation analysis showed significant correlations between IL-17 and IL-6 and TGF-β and between IL-17 and IL-21 and IL-23. The present study demonstrates that Th17 plays a role in promoting rat liver allograft rejection.

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A pathogenic role of IL- 17 at the early stage of corneal allograft rejection

Cited by 66 publications

References 40 publications

High-mobility group box 1 promotes early acute allograft rejection by enhancing IL-6-dependent Th17 alloreactive response

High-mobility group box 1 promotes early acute allograft rejection by enhancing IL-6-dependent Th17 alloreactive response

Interleukin-17 Accelerates Allograft Rejection by Suppressing Regulatory T Cell Expansion

Th17 promotes acute rejection following liver transplantation in rats

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