Cathelicidin-Related Antimicrobial Peptide Regulates CD73 Expression in Mouse Th17 Cells via p38

被引：8

作者：

Lee, Jeonghyun ^{[1
]}

Shin, Kyong-Oh ^{[2
,3
]}

Kim, Yesol ^{[1
]}

Cho, Jaewon ^{[4
]}

Lim, Hyung W. ^{[5
]}

Yoon, Sung-Il ^{[1
,6
]}

Lee, Geun-Shik ^{[6
,7
]}

Ko, Hyun-Jeong ^{[4
]}

Kim, Pyeung-Hyeun ^{[6
,8
]}

Uchida, Yoshikazu ^{[9
,10
]}

Park, Kyungho ^{[2
,3
]}

Kang, Seung Goo ^{[1
,6
]}

机构：

[1] Kangwon Natl Univ, Coll Biomed Sci, Div Biomed Convergence, Chunchon 24341, South Korea

[2] Hallym Univ, Dept Food Sci & Nutr, Chunchon 24252, South Korea

[3] Hallym Univ, Convergence Program Mat Sci Med & Pharmaceut, Chunchon 24252, South Korea

[4] Kangwon Natl Univ, Coll Pharm, Chunchon 24341, South Korea

[5] Univ Calif San Francisco, Sch Med, Gladstone Inst Virol & Immunol, Gladstone Inst Neurol Dis,Dept Neurol, San Francisco, CA 94158 USA

[6] Kangwon Natl Univ, Inst Biosci & Biotechnol, Chunchon 24341, South Korea

[7] Kangwon Natl Univ, Coll Vet Med, Chunchon 24341, South Korea

[8] Kangwon Natl Univ, Sch Biomed Sci, Dept Mol Biosci, Chunchon 24341, South Korea

[9] Univ Calif San Francisco, Sch Med, Dept Dermatol, San Francisco, CA 94212 USA

[10] Vet Affairs Med Ctr, Northern Calif Inst Res & Educ, San Francisco, CA 94212 USA

来源：

CELLS | 2020年 / 9卷 / 06期

基金：

新加坡国家研究基金会;

关键词：

CRAMP; antimicrobial peptide; CD73; adenosine; Th17; cells; TGF-beta; p38; T-CELLS; LL-37; IMMUNITY; GROWTH; TRANSCRIPTION; RECRUITMENT; ACTIVATION; MECHANISMS; ADENOSINE; PROMOTER;

D O I：

10.3390/cells9061561

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The effector function of tumor-infiltrated CD4(+)T cells is readily suppressed by many types of immune regulators in the tumor microenvironment, which is one of the major mechanisms of immune tolerance against cancer. Cathelicidin-related antimicrobial peptide (CRAMP), the mouse analog of LL-37 peptide in humans, is a cationic antimicrobial peptide belonging to the cathelicidin family; however, its secretion by cancer cells and role in the tumor microenvironment (TME) remain unclear. In this study, we explored the possibility of an interaction between effector CD4(+)T cells and CRAMP using in vitro-generated mouse Th17 cells. We found that CRAMP stimulates Th17 cells to express the ectonucleotidase CD73, while simultaneously inducing cell death. This finding suggested that CD73-expressing Th17 cells may function as immune suppressor cells instead of effector cells. In addition, treatment of pharmacological inhibitors of the transforming growth factor-beta (TGF-beta) signaling pathway showed that induction of CD73 expression is mediated by the p38 signaling pathway. Overall, our findings suggest that tumor-derived LL-37 likely functions as an immune suppressor that induces immune tolerance against tumors through shaping effector Th17 cells into suppressor Th17 cells, suggesting a new intervention target to improve cancer immunotherapy.

引用

页数：13

共 45 条

[1] CD4+ T Cell Help Confers a Cytotoxic T Cell Effector Program Including Coinhibitory Receptor Downregulation and Increased Tissue Invasiveness [J].