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High dosage of zinc modulates T-cells in a time-dependent manner within porcine gut-associated lymphatic tissue
- Kreuzer-Redmer, Susanne, Arends, Danny, Schulte, Jasper N., Karweina, Diana, Korkuc, Paula, Wöltje, Nadine, Hesse, Deike, Pieper, Robert, Gerdts, Volker, Zentek, Jürgen, Meurens, Francois, Brockmann, Gudrun A.
- The British journal of nutrition 2018 v.120 no.12 pp. 1349-1358
- CD4-positive T-lymphocytes, adaptive immunity, cytokines, diarrhea, diet, feed additives, genes, immune response, interferon-gamma, lymphatic system, piglets, zinc
- Zn serves as a powerful feed additive to reduce post-weaning diarrhoea in pigs. However, the mechanisms responsible for Zn-associated effects on the adaptive immune responses following feeding of a very high dosage of Zn remain elusive. In this study, we examined the T-cell response in gut-associated lymphatic tissues of seventy-two weaned piglets. Piglets received diets with 57 mg Zn/kg (low Zn concentration, LZn), 164 mg Zn/kg (medium Zn concentration, MZn) or 2425 mg Zn/kg (high Zn concentration, HZn) mg Zn/kg feed for 1, 2 or 4 weeks. We observed that feeding the HZn diet for 1 week increased the level of activated T-helper cells (CD4⁺ and CD8α ᵈⁱᵐ) compared with feeding MZn and LZn (P<0·05). In addition, we observed higher transcript amounts of interferon γ and T-box 21 (TBET) in the HZn group compared with the MZn and LZn groups (P<0·05). A gene set enrichment analysis revealed an over-representation of genes associated with ‘cytokine signalling in immune system’. Remarkably, feeding of a very high Zn dosage led to a switch in the immune response after 2 weeks. We detected higher relative cell counts of CD4⁺CD25ʰⁱᵍʰ regulatory T-helper cells (P<0·05) and a higher expression of forkhead box P3 (FOXP3) transcripts (P<0·05). After 4 weeks of feeding a high-dosage Zn diet, the relative CD4⁺ T-cell count (P<0·05) and the relative CD8β ⁺ T-cell count (P<0·1) were reduced compared with the MZn group. We hypothesise that after 1 week the cellular T-helper 1 response is switched on and after 2 weeks it is switched off, leading to decreased numbers of T-cells.