Regulation of chitinase-3-like-1 in T cell elicits Th1 and cytotoxic responses to inhibit lung metastasis

Do Hyun Kim, Hong Jai Park, Sangho Lim, Ja Hyun Koo, Hong Gyun Lee, Jin Ouk Choi, Ji Hoon Oh, Sang Jun Ha, Min Jong Kang, Chang Min Lee, Chun Geun Lee, Jack A. Elias, Je Min Choi

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

Chitinase-3-like-1 (Chi3l1) is known to play a significant role in the pathogenesis of Type 2 inflammation and cancer. However, the function of Chi3l1 in T cell and its clinical implications are largely unknown. Here we show that Chi3l1 expression was increased in activated T cells, especially in Th2 cells. In addition, Chi3l1-deficient T cells are hyper-responsive to TcR stimulation and are prone to differentiating into Th1 cells. Chi3l1-deficient Th1 cells show increased expression of anti-tumor immunity genes and decreased Th1 negative regulators. Deletion of Chi3l1 in T cells in mice show reduced melanoma lung metastasis with increased IFNγ and TNFα-producing T cells in the lung. Furthermore, silencing of Chi3l1 expression in the lung using peptide-siRNA complex (dNP2-siChi3l1) efficiently inhibit lung metastasis with enhanced Th1 and CTL responses. Collectively, this study demonstrates Chi3l1 is a regulator of Th1 and CTL which could be a therapeutic target to enhance anti-tumor immunity.

Original languageEnglish
Article number503
JournalNature communications
Volume9
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

Bibliographical note

Funding Information:
This research was supported by the Basic Science Research Program (NRF-2013R1A1A2A10060048) and the Bio and Medical Technology Development Program (NRF-2017M3A9C8027972) of the NRF funded by the Korean government. This work was also in part supported by grant PO1 HL114501, and R01 HL115813 from National Institute of Health (NIH), USA. We also thank Yeon-Ho Kim for technical support of FACS sorting at Hanyang LINC analytical Equipment Center (Seoul).

Publisher Copyright:
© 2018 The Author(s).

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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