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Regulating T-cell differentiation through the polyamine spermidine

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Item Type:Article
Title:Regulating T-cell differentiation through the polyamine spermidine
Creators Name:Carriche, G.M. and Almeida, L. and Stüve, P. and Velasquez, L. and Dhillon-LaBrooy, A. and Roy, U. and Lindenberg, M. and Strowig, T. and Plaza-Sirvent, C. and Schmitz, I. and Lochner, M. and Simon, A.K. and Sparwasser, T.
Abstract:BACKGROUND: The cross-talk between the host and its microbiota plays a key role in the promotion of health. The production of metabolites such as polyamines by intestinal-resident bacteria is part of this symbiosis shaping host immunity. The polyamines putrescine, spermine, and spermidine are abundant within the gastrointestinal tract and might substantially contribute to gut immunity. OBJECTIVE: We aimed to characterize the polyamine spermidine as a modulator of T-cell differentiation and function. METHODS: Naive T cells were isolated from wild-type mice or cord blood from healthy donors and submitted to polarizing cytokines, with and without spermidine treatment, to evaluate CD4(+) T-cell differentiation in vitro. Moreover, mice were subjected to oral supplementation of spermidine, or its precursor l-arginine, to assess the frequency and total numbers of regulatory T (Treg) cells in vivo. RESULTS: Spermidine modulates CD4(+) T-cell differentiation in vitro, preferentially committing naive T cells to a regulatory phenotype. After spermidine treatment, activated T cells lacking the autophagy gene Atg5 fail to upregulate Foxp3 to the same extent as wild-type cells. These results indicate that spermidine's polarizing effect requires an intact autophagic machinery. Furthermore, dietary supplementation with spermidine promotes homeostatic differentiation of Treg cells within the gut and reduces pathology in a model of T-cell transfer-induced colitis. CONCLUSION: Altogether, our results highlight the beneficial effects of spermidine, or l-arginine, on gut immunity by promoting Treg cell development.
Keywords:Polyamines, Spermidine, Gut Immunity, Treg Cells, T(H)17 Cells, Animals, Mice
Source:Journal of Allergy and Clinical Immunology
Page Range:335-348
Date:January 2021
Official Publication:https://doi.org/10.1016/j.jaci.2020.04.037
PubMed:View item in PubMed

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