PMID- 31783404
OWN - NLM
STAT- MEDLINE
DCOM- 20210517
LR  - 20210517
IS  - 1876-4479 (Electronic)
IS  - 1873-9946 (Linking)
VI  - 14
IP  - 6
DP  - 2020 Jul 9
TI  - Zinc Deficiency Activates the IL-23/Th17 Axis to Aggravate Experimental Colitis 
      in Mice.
PG  - 856-866
LID - 10.1093/ecco-jcc/jjz193 [doi]
AB  - BACKGROUND AND AIMS: Patients with inflammatory bowel disease [IBD], especially 
      Crohn's disease, often develop zinc deficiency. However, the precise mechanisms 
      by which zinc deficiency affects IBD pathology, particularly intestinal 
      macrophage function, remain unclear. We studied the effects of zinc deficiency on 
      the development and progression of colitis in mice. METHODS: To induce colitis, 
      mice were treated with 2,4,6-trinitrobenzene sulphonic acid. Rag1-/- mice were 
      then given injections of naive CD4+CD62L+ T cells. The respective degrees of 
      mucosal injury of mice that had received a zinc chelator (TPEN; 
      N,N,N',N'-tetrakis [2-pyridylmethyl]ethylenediamine) and of control mice were 
      subsequently compared. Colonic lamina propria mononuclear cells were isolated by 
      enzymatic digestion and were examined using flow cytometry. To generate mouse 
      bone marrow-derived macrophages [BMDMs], bone marrow cells were stimulated with 
      mouse macrophage-colony stimulating factor. RESULTS: Zinc deficiency aggravates 
      colonic inflammation through the activation of type 17 helper T [Th17] cells in 
      mice. Flow cytometric analysis revealed that zinc deficiency significantly 
      increases the proportion of pro-inflammatory [M1] macrophages in colonic lamina 
      propria mononuclear cells obtained from inflamed colon. Interferon-gamma plus 
      lipopolysaccharide-mediated M1 skewing alters the expression of zinc transporters 
      in BMDMs and thereby decreases the intracellular free zinc. TPEN treatment 
      mimicking the effects of the M1 skewing up-regulates IL-23p19 expression, which 
      is strongly related to Th17 development. Furthermore, the nuclear accumulation of 
      interferon-regulatory factor 5 is closely involved in IL-23p19 induction in 
      zinc-deficient macrophages. CONCLUSIONS: Zinc deficiency aggravates colonic 
      inflammation through activation of the IL-23/Th17 axis. This activation is 
      controlled by subcellular distribution of interferon-regulatory factor 5.
CI  - Copyright (c) 2019 European Crohn's and Colitis Organisation (ECCO). Published by 
      Oxford University Press. All rights reserved. For permissions, please email: 
      journals.permissions@oup.com.
FAU - Higashimura, Yasuki
AU  - Higashimura Y
AD  - Department of Food Science, Ishikawa Prefectural University, Nonoichi, Ishikawa, 
      Japan.
FAU - Takagi, Tomohisa
AU  - Takagi T
AD  - Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, 
      Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan.
AD  - Department for Medical Innovation and Translational Medical Science, Graduate 
      School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 
      Kyoto, Japan.
FAU - Naito, Yuji
AU  - Naito Y
AD  - Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, 
      Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan.
FAU - Uchiyama, Kazuhiko
AU  - Uchiyama K
AD  - Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, 
      Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan.
FAU - Mizushima, Katsura
AU  - Mizushima K
AD  - Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, 
      Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan.
FAU - Tanaka, Makoto
AU  - Tanaka M
AD  - Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, 
      Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan.
FAU - Hamaguchi, Masahide
AU  - Hamaguchi M
AD  - Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto 
      Prefectural University of Medicine, Kyoto, Kyoto, Japan.
FAU - Itoh, Yoshito
AU  - Itoh Y
AD  - Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, 
      Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan.
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Crohns Colitis
JT  - Journal of Crohn's & colitis
JID - 101318676
RN  - 0 (Carrier Proteins)
RN  - 0 (Chelating Agents)
RN  - 0 (Ethylenediamines)
RN  - 0 (Interleukin-23)
RN  - 0 (Trace Elements)
RN  - 0 (zinc-binding protein)
RN  - J41CSQ7QDS (Zinc)
RN  - R9PTU1U29I (N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine)
SB  - IM
MH  - Animals
MH  - Carrier Proteins/metabolism
MH  - Chelating Agents/pharmacology
MH  - Deficiency Diseases/immunology
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Ethylenediamines/pharmacology
MH  - *Inflammatory Bowel Diseases/immunology/metabolism/pathology
MH  - Interleukin-23/immunology
MH  - *Intestinal Mucosa/immunology/pathology
MH  - *Macrophages/immunology/metabolism
MH  - Mice
MH  - Th17 Cells/immunology
MH  - Trace Elements/deficiency/immunology/metabolism
MH  - *Zinc/deficiency/immunology/metabolism
OTO - NOTNLM
OT  - Inflammatory bowel disease
OT  - lymphocytes
OT  - macrophages
EDAT- 2019/11/30 06:00
MHDA- 2021/05/18 06:00
CRDT- 2019/11/30 06:00
PHST- 2019/11/30 06:00 [pubmed]
PHST- 2021/05/18 06:00 [medline]
PHST- 2019/11/30 06:00 [entrez]
AID - 5648054 [pii]
AID - 10.1093/ecco-jcc/jjz193 [doi]
PST - ppublish
SO  - J Crohns Colitis. 2020 Jul 9;14(6):856-866. doi: 10.1093/ecco-jcc/jjz193.