Cathelicidin-Related Antimicrobial Peptide Regulates CD73 Expression in Mouse Th17 Cells via p38
The effector function of tumor-infiltrated CD4<sup>+</sup> 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 mous...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2020-06-01
|
Series: | Cells |
Subjects: | |
Online Access: | https://www.mdpi.com/2073-4409/9/6/1561 |
id |
doaj-792589cfda1e409c94fa9496130a61d6 |
---|---|
record_format |
Article |
spelling |
doaj-792589cfda1e409c94fa9496130a61d62020-11-25T02:45:34ZengMDPI AGCells2073-44092020-06-0191561156110.3390/cells9061561Cathelicidin-Related Antimicrobial Peptide Regulates CD73 Expression in Mouse Th17 Cells via p38Jeonghyun Lee0Kyong-Oh Shin1Yesol Kim2Jaewon Cho3Hyung W. Lim4Sung-Il Yoon5Geun-Shik Lee6Hyun-Jeong Ko7Pyeung-Hyeun Kim8Yoshikazu Uchida9Kyungho Park10Seung Goo Kang11Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24341, KoreaDepartment of Food Science and Nutrition, and Convergence Program of Material Science for Medicine and Pharmaceutics, Hallym University, Chuncheon 24252, KoreaDivision of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24341, KoreaCollege of Pharmacy, Kangwon National University, Chuncheon 24341, KoreaGladstone Institute of Virology and Immunology, Gladstone Institute of Neurological Disease, School of Medicine, Department of Neurology, University of California, San Francisco, CA 94158, USADivision of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24341, KoreaInstitute of Bioscience & Biotechnology, Kangwon National University, Chuncheon 24341, KoreaCollege of Pharmacy, Kangwon National University, Chuncheon 24341, KoreaInstitute of Bioscience & Biotechnology, Kangwon National University, Chuncheon 24341, KoreaDepartment of Dermatology, School of Medicine, University of California, San Francisco and Northern California Institute for Research and Education, Veterans Affairs Medical Center, San Francisco, CA 94212, USADepartment of Food Science and Nutrition, and Convergence Program of Material Science for Medicine and Pharmaceutics, Hallym University, Chuncheon 24252, KoreaDivision of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24341, KoreaThe effector function of tumor-infiltrated CD4<sup>+</sup> 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<sup>+</sup> 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-β) 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.https://www.mdpi.com/2073-4409/9/6/1561CRAMPantimicrobial peptideCD73adenosineTh17 cellsTGF-beta |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jeonghyun Lee Kyong-Oh Shin Yesol Kim Jaewon Cho Hyung W. Lim Sung-Il Yoon Geun-Shik Lee Hyun-Jeong Ko Pyeung-Hyeun Kim Yoshikazu Uchida Kyungho Park Seung Goo Kang |
spellingShingle |
Jeonghyun Lee Kyong-Oh Shin Yesol Kim Jaewon Cho Hyung W. Lim Sung-Il Yoon Geun-Shik Lee Hyun-Jeong Ko Pyeung-Hyeun Kim Yoshikazu Uchida Kyungho Park Seung Goo Kang Cathelicidin-Related Antimicrobial Peptide Regulates CD73 Expression in Mouse Th17 Cells via p38 Cells CRAMP antimicrobial peptide CD73 adenosine Th17 cells TGF-beta |
author_facet |
Jeonghyun Lee Kyong-Oh Shin Yesol Kim Jaewon Cho Hyung W. Lim Sung-Il Yoon Geun-Shik Lee Hyun-Jeong Ko Pyeung-Hyeun Kim Yoshikazu Uchida Kyungho Park Seung Goo Kang |
author_sort |
Jeonghyun Lee |
title |
Cathelicidin-Related Antimicrobial Peptide Regulates CD73 Expression in Mouse Th17 Cells via p38 |
title_short |
Cathelicidin-Related Antimicrobial Peptide Regulates CD73 Expression in Mouse Th17 Cells via p38 |
title_full |
Cathelicidin-Related Antimicrobial Peptide Regulates CD73 Expression in Mouse Th17 Cells via p38 |
title_fullStr |
Cathelicidin-Related Antimicrobial Peptide Regulates CD73 Expression in Mouse Th17 Cells via p38 |
title_full_unstemmed |
Cathelicidin-Related Antimicrobial Peptide Regulates CD73 Expression in Mouse Th17 Cells via p38 |
title_sort |
cathelicidin-related antimicrobial peptide regulates cd73 expression in mouse th17 cells via p38 |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2020-06-01 |
description |
The effector function of tumor-infiltrated CD4<sup>+</sup> 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<sup>+</sup> 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-β) 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. |
topic |
CRAMP antimicrobial peptide CD73 adenosine Th17 cells TGF-beta |
url |
https://www.mdpi.com/2073-4409/9/6/1561 |
work_keys_str_mv |
AT jeonghyunlee cathelicidinrelatedantimicrobialpeptideregulatescd73expressioninmouseth17cellsviap38 AT kyongohshin cathelicidinrelatedantimicrobialpeptideregulatescd73expressioninmouseth17cellsviap38 AT yesolkim cathelicidinrelatedantimicrobialpeptideregulatescd73expressioninmouseth17cellsviap38 AT jaewoncho cathelicidinrelatedantimicrobialpeptideregulatescd73expressioninmouseth17cellsviap38 AT hyungwlim cathelicidinrelatedantimicrobialpeptideregulatescd73expressioninmouseth17cellsviap38 AT sungilyoon cathelicidinrelatedantimicrobialpeptideregulatescd73expressioninmouseth17cellsviap38 AT geunshiklee cathelicidinrelatedantimicrobialpeptideregulatescd73expressioninmouseth17cellsviap38 AT hyunjeongko cathelicidinrelatedantimicrobialpeptideregulatescd73expressioninmouseth17cellsviap38 AT pyeunghyeunkim cathelicidinrelatedantimicrobialpeptideregulatescd73expressioninmouseth17cellsviap38 AT yoshikazuuchida cathelicidinrelatedantimicrobialpeptideregulatescd73expressioninmouseth17cellsviap38 AT kyunghopark cathelicidinrelatedantimicrobialpeptideregulatescd73expressioninmouseth17cellsviap38 AT seunggookang cathelicidinrelatedantimicrobialpeptideregulatescd73expressioninmouseth17cellsviap38 |
_version_ |
1724761771233771520 |