Alanyl-glutamine resolves lipopolysaccharide-induced lung injury in mice by modulating the polarization of regulatory T cells and T helper 17 cells

Abstract

Regulatory T cells (Tregs) and T helper (Th) 17 cells are two subsets of Th cells with opposing actions which participate in the process of resolving acute lung injury (ALI). Glutamine (Gln) is a nutrient commonly used in nutrition regimens due to its immunomodulatory effects. This study investigated whether alanyl-glutamine (Ala-Gln) administration modulated polarization of Th subsets in a model of lipopolysaccharide (LPS)-induced ALI during the resolution period. Intratracheal instillation of LPS in male C57BL/6J mice was used to induce ALI. On day 1 after LPS instillation, mice in the Gln group were given an intragastric gavage of 0.75 g Ala-Gln/kg daily, whereas the control (Con) group received identical amounts of sterilized distilled water. At 4, 7 and 10 days after a single dose of LPS, mice were killed by cardiac puncture. Bronchoalveolar lavage (BAL) fluid and lung tissues were collected for further analysis. Compared to the Con group, weight loss was less in the Gln group. Percentages of Tregs and interleukin-2 levels in BAL fluid increased, whereas Th17 cells were suppressed in the Gln group. Neutrophil clearance was promoted in the Gln group. Expressions of proinflammatory-related and fibrosis-related genes in lung tissues decreased in the Gln group. Histopathological findings also showed that interstitial inflammation was less severe in the Gln group. These results suggest that Ala-Gln administration after the onset of ALI can help resolve lung inflammation and injury by modulating the polarization of Tregs and Th17 cells.

Keywords: Acute lung injury; Glutamine; Lipopolysaccharide; Regulatory T cells; T helper 17 cells.