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Prophylaxis of acute graft-versus-host disease by CCR5 blockade combined with cyclosporine A in a murine model

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Abstract

Objective

One characteristic feature of graft-versus-host disease (GVHD) is lymphocytes’ trafficking and recruitment to target tissues, and CCR5 plays a key role in the process. Thus, blockade of lymphocytes’ chemotaxis may attenuate GVHD.

Methods

We tested the effects of CCR5 blockade using an established murine model. The mean survival time, body weight change, and clinical GVHD scores were assessed. Concentrations of cytokines and chemokines, the CCR5, CXCR3, and CCR7 expressions on T lymphocytes, and histological changes of visceral organs were also evaluated. Additionally, we assessed the immunophenotype of infiltration cells in liver and intestine.

Results

Mice undergoing total body irradiation and allogenic hematopoietic stem cell transplantation (allo-HSCT) developed typical GVHD. MVC increased CCR5 expression whereas CCR7 and CXCR3 expression were unaffected. MVC also increased plasma levels of the ligands of CCR5. A combination of MVC with CsA significantly alleviated the degree of visceral injuries and prolonged survival time.

Conclusion

MVC has a synergistic effect with CsA. It can attenuate the severity of GVHD and increase survival rate of mice in our murine model. This may offer a novel therapeutic perspective for clinical GVHD after allo-HSCT.

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Acknowledgments

This study was financially supported by the National Natural Science Foundation of China (No. 81370667).

Conflict of interest

The authors have declared that no competing interests exist.

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Authors and Affiliations

  1. Department of Hematology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China

    Jing Yuan, Han-yun Ren, Yong-jin Shi & Wei Liu

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  1. Jing Yuan
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  2. Han-yun Ren
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  3. Yong-jin Shi
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  4. Wei Liu
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Corresponding author

Correspondence to Han-yun Ren.

Additional information

Responsible Editor: Liwu Li.

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Yuan, J., Ren, Hy., Shi, Yj. et al. Prophylaxis of acute graft-versus-host disease by CCR5 blockade combined with cyclosporine A in a murine model. Inflamm. Res. 64, 137–144 (2015). https://doi.org/10.1007/s00011-014-0793-6

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  • DOI: https://doi.org/10.1007/s00011-014-0793-6

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