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Inflammation

, Volume 40, Issue 5, pp 1576–1588 | Cite as

Chitinase 3-Like-1-Deficient Splenocytes Deteriorated the Pathogenesis of Acute Graft-Versus-Host Disease via Regulating Differentiation of Tfh Cells

  • Zengyao Li
  • Hao Lu
  • Jian Gu
  • Jing Liu
  • Qin Zhu
  • Yunjie Lu
  • Xuehao WangEmail author
ORIGINAL ARTICLE

Abstract

Acute graft-versus-host disease (aGVHD) is an intractable complication in transplant patients, limiting the efficacy of this therapy. Chitinase 3-like-1 (CHI3L1), a member of the glycosyl hydrolase 18 family that lacks chitinase activity, plays a critical role in a variety of inflammatory diseases. Here, we investigated the in vitro and in vivo effects of CHI3L1 on the development of aGVHD. In this study, mixed lymphocyte reactions (MLR) in vitro showed that CHI3L1 deficiency in CD4+ T cell promoted the production of interferon (IFN)-γ and T follicular helper (Tfh)-related cytokines such as interleukin-6 (IL-6) and interleukin-21 (IL-21). Meanwhile, the inducible Tfh cell population increased remarkably in CHI3L1-KO CD4+ T cells’ induction group, compared with WT group. Then, in the murine acute GVHD model, we found that CHI3L1 deficiency in donor splenocytes dramatically increased the severity of aGVHD through enhancing Tfh cell differentiation. Moreover, at mRNA and protein levels, we defined several molecules that may account for the enhanced ability of CHI3L1-KO splenocytes to migrate into target organs and produce IFN-γ and Tfh-related cytokines and chemokines, such as IL-6, IL-21, and CXCL13. Expression of inducible co-stimulator (ICOS) and B cell lymphoma 6 (Bcl6) increased in the skin, the intestine, the lung, and the liver from CHI3L1-KO splenocyte-treated aGVHD mice. Therefore, these results strongly imply that CHI3L1 levels in donor cells may be related to the risk of aGVHD and targeting CHI3L1 represents a novel therapeutic strategy for controlling aGVHD progression.

KEY WORDS

CHI3L1 aGVHD transplantation 

Notes

Acknowledgements

This work was supported by the National Natural Science Fund 81509236 (XHW), the National Natural Science Fund Outstanding Youth Fund 81522020 (LL), the 863 Young Scientists Special Fund 81522020 (LL), and the National Natural Science Fund 91442117 and 81571564 (LL) in China as well as Jiangsu Province’s Outstanding Medical Academic Key Program RC2016 (LL).

Compliance with Ethical Standards

The protocols used in this study were approved by the Institutional Animal Care and Use Committees at Nanjing Medical University.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Zengyao Li
    • 1
  • Hao Lu
    • 1
  • Jian Gu
    • 1
  • Jing Liu
    • 2
  • Qin Zhu
    • 1
  • Yunjie Lu
    • 1
  • Xuehao Wang
    • 1
    Email author
  1. 1.Liver Transplantation Center, First Affiliated HospitalNanjing Medical UniversityNanjingChina
  2. 2.Department of Radiotherapy, First Affiliated HospitalNanjing Medical UniversityNanjingChina

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