PMID- 35547774
OWN - NLM
STAT- MEDLINE
DCOM- 20220517
LR  - 20221207
IS  - 1838-7640 (Electronic)
IS  - 1838-7640 (Linking)
VI  - 12
IP  - 7
DP  - 2022
TI  - Cathelicidin-related antimicrobial peptide protects against enteric 
      pathogen-accelerated type 1 diabetes in mice.
PG  - 3438-3455
LID - 10.7150/thno.61433 [doi]
AB  - Rationale: Gut barrier disruption caused by enteric pathogen infection results in 
      activated diabetogenic T cells and accelerated type 1 diabetes (T1D). 
      Cathelicidin-related antimicrobial peptide (CRAMP) maintains intestinal barrier 
      integrity, regulates the microbiome, and exerts positive immune-modulatory 
      effects on pancreatic diseases. Methods: The model enteric pathogen Citrobacter 
      rodentium (C. rodentium) was adopted to represent clinical colonic infection with 
      gut barrier disruption. The protective role and gut-pancreas pathophysiological 
      mechanism of CRAMP in enteric pathogen-accelerated T1D were investigated in 
      spontaneous non-obese diabetic (NOD) mice and streptozotocin-induced diabetic 
      mice. Results: Colonic CRAMP production was defective in C. rodentium 
      infection-accelerated T1D. C. rodentium infection triggered the recruitment of 
      interferon-gamma (IFN-gamma)(+) T cells and accelerated T1D. In the C. 
      rodentium-accelerated T1D mice, CRAMP deficiency further aggravated gut barrier 
      disruption, gut dysbiosis, and diabetic phenotype, which could be reversed by 
      CRAMP treatment. The protective effect of CRAMP may be due to CRAMP inhibiting C. 
      rodentium-aggravated gut immune dysregulation, gut dysbiosis, and migration of 
      gut-primed IFN-gamma(+) T cells to the pancreas, thus contributing to gut barrier 
      protection and pancreatic-intestinal immune homeostasis. Conclusion: CRAMP plays 
      a pivotal role in pancreatic-gut crosstalk during C. rodentium-accelerated T1D by 
      gut barrier-protective, immune- and microbial-modulatory mechanisms. Cathelicidin 
      supplementation to restore a healthy gut barrier may represent a novel 
      therapeutic strategy for T1D.
CI  - (c) The author(s).
FAU - Jia, Lingling
AU  - Jia L
AD  - Wuxi School of Medicine and School of Food Science and Technology, Jiangnan 
      University, Wuxi 214122, Jiangsu, P. R. China.
AD  - State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 
      214122, Jiangsu, P. R. China.
AD  - College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo 315800, 
      Zhejiang, P. R. China.
FAU - Li, Jiahong
AU  - Li J
AD  - Wuxi School of Medicine and School of Food Science and Technology, Jiangnan 
      University, Wuxi 214122, Jiangsu, P. R. China.
FAU - Zhang, Ming
AU  - Zhang M
AD  - Wuxi School of Medicine and School of Food Science and Technology, Jiangnan 
      University, Wuxi 214122, Jiangsu, P. R. China.
FAU - Liu, He
AU  - Liu H
AD  - Wuxi School of Medicine and School of Food Science and Technology, Jiangnan 
      University, Wuxi 214122, Jiangsu, P. R. China.
FAU - Ren, Zhengnan
AU  - Ren Z
AD  - Wuxi School of Medicine and School of Food Science and Technology, Jiangnan 
      University, Wuxi 214122, Jiangsu, P. R. China.
FAU - Dong, Xiao Liang
AU  - Dong XL
AD  - Wuxi School of Medicine and School of Food Science and Technology, Jiangnan 
      University, Wuxi 214122, Jiangsu, P. R. China.
FAU - Pan, Xiaohua
AU  - Pan X
AD  - Wuxi School of Medicine and School of Food Science and Technology, Jiangnan 
      University, Wuxi 214122, Jiangsu, P. R. China.
FAU - Qiu, Ju
AU  - Qiu J
AD  - CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of 
      Nutrition and Health, Shanghai Institutes for Biological Sciences, University of 
      Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, P. R. 
      China.
FAU - Pan, Li-Long
AU  - Pan LL
AD  - Wuxi School of Medicine and School of Food Science and Technology, Jiangnan 
      University, Wuxi 214122, Jiangsu, P. R. China.
FAU - Sun, Jia
AU  - Sun J
AD  - Wuxi School of Medicine and School of Food Science and Technology, Jiangnan 
      University, Wuxi 214122, Jiangsu, P. R. China.
AD  - State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 
      214122, Jiangsu, P. R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220424
PL  - Australia
TA  - Theranostics
JT  - Theranostics
JID - 101552395
RN  - 0 (Antimicrobial Cationic Peptides)
RN  - 0 (Antimicrobial Peptides)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 0 (Cathelicidins)
SB  - IM
MH  - Animals
MH  - Antimicrobial Cationic Peptides
MH  - Antimicrobial Peptides
MH  - Citrobacter rodentium/physiology
MH  - *Diabetes Mellitus, Experimental
MH  - *Diabetes Mellitus, Type 1
MH  - Dysbiosis
MH  - *Gastrointestinal Microbiome
MH  - Interferon-gamma
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred NOD
MH  - Cathelicidins
PMC - PMC9065195
OTO - NOTNLM
OT  - antimicrobial peptides
OT  - gut barrier
OT  - gut-pancreas crosstalk
OT  - intestinal IFNgamma+ T cell migration
OT  - type 1 diabetes
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2022/05/14 06:00
MHDA- 2022/05/18 06:00
PMCR- 2022/01/01
CRDT- 2022/05/13 11:17
PHST- 2021/04/09 00:00 [received]
PHST- 2022/01/25 00:00 [accepted]
PHST- 2022/05/13 11:17 [entrez]
PHST- 2022/05/14 06:00 [pubmed]
PHST- 2022/05/18 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - thnov12p3438 [pii]
AID - 10.7150/thno.61433 [doi]
PST - epublish
SO  - Theranostics. 2022 Apr 24;12(7):3438-3455. doi: 10.7150/thno.61433. eCollection 
      2022.