Journal
JOURNAL OF PARENTERAL AND ENTERAL NUTRITION
Volume 46, Issue 6, Pages 1371-1383Publisher
WILEY
DOI: 10.1002/jpen.2313
Keywords
MUC2; occludin; regulatory T cell; T helper cell; ZO-1
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Funding
- Mini-Invasive Surgery Foundation (Taipei, Taiwan) [110-2]
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This study investigated the effect of calcitriol treatment on CD4(+) T-cell polarization and intestinal injury in obese mice with sepsis. The results demonstrated that calcitriol treatment can balance CD4 T-cell subsets and alleviate intestinal inflammation and injury in obese mice complicated with sepsis.
Background Sepsis is a lethal syndrome with T-cell dysregulation, imbalanced inflammatory reactions, and gastrointestinal dysfunction. Obesity coexistent with sepsis can cause more-deleterious disease outcomes. Vitamin D is a nutrient with immunomodulatory ability and helps maintain intestinal homeostasis. This study investigated treatment with calcitriol on mesenteric lymph node (MLN) CD4(+) T-cell polarization and intestinal injury in obese mice with sepsis. Methods Mice received a high-fat diet for 10 weeks; then, mice were separated into an obese control group without sepsis and sepsis groups that underwent cecal ligation and puncture (CLP). Septic mice were subdivided into a group that was injected with saline (SS group) or a group that was injected with calcitriol (SD group) via a tail vein 1 h after CLP. Obese mice with sepsis were euthanized at 12 or 24 h post CLP. Results Sepsis resulted in increased percentages of type 2 T helper (Th2), Th17, and regulatory T (Treg) cells in MLNs. Also, inflammation-associated genes were upregulated and tight junction genes downregulated in the intestines after CLP. Compared with the SS group, the SD group exhibited reduced Th2, Th17, and Treg percentages in MLNs. Also, intestinal inflammatory chemokine expressions were reduced, whereas MUC2, ZO-1, and occludin had increased after CLP. Lower inflammatory cytokine levels in peritoneal lavage fluid in the ileum were also noted in the SD group. Conclusions Intravenous calcitriol treatment after sepsis can elicit more-balanced CD4 T-cell subsets in lymph nodes near the intestines and alleviate intestinal inflammation and injury in obese mice complicated with sepsis.
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