PMID- 32604872
OWN - NLM
STAT- MEDLINE
DCOM- 20210331
LR  - 20210331
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 9
IP  - 6
DP  - 2020 Jun 26
TI  - Cathelicidin-Related Antimicrobial Peptide Regulates CD73 Expression in Mouse 
      Th17 Cells via p38.
LID - 10.3390/cells9061561 [doi]
LID - 1561
AB  - 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.
FAU - Lee, Jeonghyun
AU  - Lee J
AD  - Division of Biomedical Convergence, College of Biomedical Science, Kangwon 
      National University, Chuncheon 24341, Korea.
FAU - Shin, Kyong-Oh
AU  - Shin KO
AD  - Department of Food Science and Nutrition, and Convergence Program of Material 
      Science for Medicine and Pharmaceutics, Hallym University, Chuncheon 24252, 
      Korea.
FAU - Kim, Yesol
AU  - Kim Y
AD  - Division of Biomedical Convergence, College of Biomedical Science, Kangwon 
      National University, Chuncheon 24341, Korea.
FAU - Cho, Jaewon
AU  - Cho J
AD  - College of Pharmacy, Kangwon National University, Chuncheon 24341, Korea.
FAU - Lim, Hyung W
AU  - Lim HW
AD  - Gladstone Institute of Virology and Immunology, Gladstone Institute of 
      Neurological Disease, School of Medicine, Department of Neurology, University of 
      California, San Francisco, CA 94158, USA.
FAU - Yoon, Sung-Il
AU  - Yoon SI
AD  - Division of Biomedical Convergence, College of Biomedical Science, Kangwon 
      National University, Chuncheon 24341, Korea.
AD  - Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon 
      24341, Korea.
FAU - Lee, Geun-Shik
AU  - Lee GS
AD  - Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon 
      24341, Korea.
AD  - College of Veterinary Medicine, Kangwon National University, Chuncheon 24341, 
      Korea.
FAU - Ko, Hyun-Jeong
AU  - Ko HJ
AD  - College of Pharmacy, Kangwon National University, Chuncheon 24341, Korea.
FAU - Kim, Pyeung-Hyeun
AU  - Kim PH
AD  - Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon 
      24341, Korea.
AD  - Department of Molecular Bioscience, School of Biomedical Science, Kangwon 
      National University, Chuncheon 24341, Korea.
FAU - Uchida, Yoshikazu
AU  - Uchida Y
AD  - Department 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, USA.
FAU - Park, Kyungho
AU  - Park K
AUID- ORCID: 0000-0002-1552-9914
AD  - Department of Food Science and Nutrition, and Convergence Program of Material 
      Science for Medicine and Pharmaceutics, Hallym University, Chuncheon 24252, 
      Korea.
FAU - Kang, Seung Goo
AU  - Kang SG
AUID- ORCID: 0000-0003-3981-1399
AD  - Division of Biomedical Convergence, College of Biomedical Science, Kangwon 
      National University, Chuncheon 24341, Korea.
AD  - Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon 
      24341, Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200626
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Antimicrobial Cationic Peptides)
RN  - 0 (CD37 protein, human)
RN  - 0 (Tetraspanins)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Antigens, Neoplasm/*metabolism
MH  - Antimicrobial Cationic Peptides/*metabolism
MH  - Female
MH  - Humans
MH  - Mice
MH  - Tetraspanins/*metabolism
MH  - Th17 Cells/*metabolism
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
PMC - PMC7348842
OTO - NOTNLM
OT  - CD73
OT  - CRAMP
OT  - TGF-beta
OT  - Th17 cells
OT  - adenosine
OT  - antimicrobial peptide
OT  - p38
COIS- The authors declare no commercial or financial conflict of interest.
EDAT- 2020/07/02 06:00
MHDA- 2021/04/01 06:00
PMCR- 2020/06/01
CRDT- 2020/07/02 06:00
PHST- 2020/05/13 00:00 [received]
PHST- 2020/06/20 00:00 [revised]
PHST- 2020/06/24 00:00 [accepted]
PHST- 2020/07/02 06:00 [entrez]
PHST- 2020/07/02 06:00 [pubmed]
PHST- 2021/04/01 06:00 [medline]
PHST- 2020/06/01 00:00 [pmc-release]
AID - cells9061561 [pii]
AID - cells-09-01561 [pii]
AID - 10.3390/cells9061561 [doi]
PST - epublish
SO  - Cells. 2020 Jun 26;9(6):1561. doi: 10.3390/cells9061561.