Guilhermina M Carriche1, Luís Almeida1, Philipp Stüve1, Lis Velasquez1, Ayesha Dhillon-LaBrooy1, Urmi Roy2, Marc Lindenberg3, Till Strowig4, Carlos Plaza-Sirvent5, Ingo Schmitz6, Matthias Lochner7, Anna Katharina Simon8, Tim Sparwasser9. 1. Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany; Institute of Medical Microbiology and Hygiene, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany. 2. Department of Microbial Immune Regulation, Helmholtz Centre for Infection Research, Braunschweig, Germany. 3. Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany. 4. Department of Microbial Immune Regulation, Helmholtz Centre for Infection Research, Braunschweig, Germany; Hannover Medical School, Hannover, Germany. 5. Institute for Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany. 6. Institute for Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany; Systems-Oriented Immunology and Inflammation Research Group, Department of Experimental Immunology, Helmholtz Center for Infection Research, Braunschweig, Germany; Department of Molecular Immunology, Ruhr-University Bochum, Bochum, Germany. 7. Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany; Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany. 8. Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom. 9. Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany; Institute of Medical Microbiology and Hygiene, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany. Electronic address: sparwasser@uni-mainz.de.
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.
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 polyaminesputrescine, 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.
Authors: Marcin Wawrzyniak; David Groeger; Remo Frei; Ruth Ferstl; Paulina Wawrzyniak; Krzysztof Krawczyk; Benoit Pugin; Weronika Barcik; Patrick Westermann; Anita Dreher; Michael Scharl; Marek Jutel; Cezmi A Akdis; Liam O Mahony Journal: Pharmacol Res Perspect Date: 2021-08
Authors: Daniel J Puleston; Francesc Baixauli; David E Sanin; Joy Edwards-Hicks; Matteo Villa; Agnieszka M Kabat; Marcin M Kamiński; Michal Stanckzak; Hauke J Weiss; Katarzyna M Grzes; Klara Piletic; Cameron S Field; Mauro Corrado; Fabian Haessler; Chao Wang; Yaarub Musa; Lena Schimmelpfennig; Lea Flachsmann; Gerhard Mittler; Nir Yosef; Vijay K Kuchroo; Joerg M Buescher; Stefan Balabanov; Edward J Pearce; Douglas R Green; Erika L Pearce Journal: Cell Date: 2021-07-02 Impact factor: 66.850