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

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Title
Regulation of Chitinase-3-like-1 in T cell elicits Th1 and cytotoxic responses to inhibit lung metastasis
Author(s)
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
Publication Date
2018-02
Journal
NATURE COMMUNICATIONS, v.9, no.1, pp.503 -
Publisher
NATURE PUBLISHING GROUP
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.
URI
https://pr.ibs.re.kr/handle/8788114/4446
ISSN
2041-1723
Appears in Collections:
Center for Neuroscience Imaging Research (뇌과학 이미징 연구단) > Journal Papers (저널논문)
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