Zinc deficiency activates IL-23/Th17 axis to aggravate experimental colitis in mice.

Zinc deficiency activates IL-23/Th17 axis to aggravate experimental colitis in mice.

J Crohns Colitis. 2019 Nov 30;:

Authors: Higashimura Y, Takagi T, Naito Y, Uchiyama K, Mizushima K, Tanaka M, Hamaguchi M, Itoh Y

Abstract
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 zinc deficiency effects on the development and progression of colitis in mice.
METHODS: To induce colitis, mice were treated with 2,4,6-trinitrobenzene sulphonic acid. Then Rag1-/- mice were given injections of naïve CD4+CD62L+ T cells. The respective degrees of mucosal injury of mice that had received zinc chelator (TPEN;N,N,N’,N’.
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-γ 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. The activation is controlled by subcellular distribution of interferon-regulatory factor 5.

PMID: 31783404 [PubMed – as supplied by publisher]

PubMed Link: https://www.ncbi.nlm.nih.gov/pubmed/31783404?dopt=Abstract