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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.01737

Gut bacterial metabolite Urolithin A (UA) mitigates Ca2+ entry in T cells by regulating miR-10a-5p

 Yogesh Singh1*, Shaqiu Zhang2,  Tamer Al-Maghout3, 4, Icy Cao4, Lisann Pelzl4,  Madhuri Salker5,  Marc Veldhoen6,  Anchun Cheng2 and  Florian Lang4
  • 1Tübingen University Hospital, Germany
  • 2Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, China
  • 3University of Tübingen, Germany
  • 4Medizinische Fakultät, Universität Tübingen, Germany
  • 5University Women's Hospital Tübingen, Germany
  • 6University of Lisbon, Portugal

The gut microbiota influences several biological functions including immune responses. Inflammatory bowel disease is favourably influenced by consumption of several dietary natural plant products such as pomegranate, walnuts and berries containing polyphenolic compounds such as ellagitannins and ellagic acid. The gut microbiota metabolises ellagic acid resulting in the formation of bioactive urolithins A, B, C and D. Urolithin A (UA) is the most active and effective gut metabolite and acts as a potent anti-inflammatory and anti-oxidant agent. However, whether gut metabolite UA, affects the function of immune cells remains incompletely understood. T cell proliferation is stimulated by store operated Ca2+ entry (SOCE) resulting from stimulation of Orai1 by STIM1/STIM2. We show here that treatment of murine CD4+ T cells with UA (10 µM, 3 days) significantly blunted SOCE in CD4+ T cells, an effect paralleled by significant downregulation of Orai1 and STIM1/2 transcript levels and protein abundance. UA treatment further increased miR-10a-5p abundance in CD4+ T cells in a dose dependent fashion. Overexpression of miR-10a-5p significantly decreased STIM1/2 and Orai1 mRNA and protein levels as well as SOCE in CD4+ T cells. UA further decreased CD4+ T cell proliferation. Thus, the gut bacterial metabolite UA increases miR-10a-5p levels thereby regulating Orai1/STIM1/STIM2 expression, store operated Ca2+ entry and proliferation of murine CD4+ T cells.

Keywords: CD4+ T cells, Urolithin A, SOCE, Ca2+ channel, MiR-10a-5p

Received: 18 Mar 2019; Accepted: 09 Jul 2019.

Edited by:

Wilson Savino, Oswaldo Cruz Foundation (Fiocruz), Brazil

Reviewed by:

Xi Ma, China Agricultural University (CAU), China
Anna K. Kiss, Medical University of Warsaw, Poland  

Copyright: © 2019 Singh, Zhang, Al-Maghout, Cao, Pelzl, Salker, Veldhoen, Cheng and Lang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Yogesh Singh, Tübingen University Hospital, Tübingen, Germany, ysinghbt@gmail.com