Effectiveness of interleukin-4 administration or zinc supplementation in improving zinc deficiency-associated thymic atrophy and fatty degeneration and in normalizing T cell maturation process.

Abstract

Nutritional zinc deficiency induces thymic atrophy, but the underlying mechanisms remain unknown. In this study, we investigated the mechanism of thymic atrophy and fatty degeneration associated with zinc deficiency and its effect on T cell maturation. Building on previous research demonstrating the beneficial effect of IL-4 administration or zinc supplementation on the spleen in zinc-deficient rats, we further examined whether these supplements also improve thymic atrophy. Five-week-old male Sprague-Dawley rats were fed a standard diet, zinc-deficient diet (n=16 each) with either saline or IL-4, or a zinc-deficient diet for 6weeks followed by a standard diet for 4weeks. Relative thymus weights, serum thymulin concentrations, and the number of cytokeratin-8-positive cells, AIRE-positive cells, IL-7-positive cells, CD8+ T cells, CD4+ T cells, pre-T cells, and CD25+ CD44+ (DN3) cells in the thymus of zinc-deficient rats significantly decreased compared with those in all other groups. Conversely, PPAR-γ-positive cells, oil red O-positive areas, pro T cells, CD25- CD44+ cells, TUNEL-positive cells, Viobility 405/452 Fixable Dye-positive cells, CD68-, CD163- or CD169- macrophages, and IL-1β concentrations were significantly increased in the thymus of zinc-deficient rats as compared to those in the other groups. After IL-4 administration or zinc supplementation for zinc deficiency, all the measurement indices were recovered to levels in standard rats. It was demonstrated that zinc deficiency caused thymic atrophy, accompanied by fatty degeneration in the cortical regions and affected T cell maturation. IL-4 administration or zinc supplementation for zinc deficiency ameliorated thymic fatty degeneration.