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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Inflammation Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1528759
This article is part of the Research Topic Inflammation and Lipid Signaling in Disease Pathogenesis View all 7 articles

The endocannabinoid anandamide prevents TH17 programming of activated T lymphocytes while preserving TH1 responses

Provisionally accepted
Anastasiia Kiprina Anastasiia Kiprina 1Tom Teichmann Tom Teichmann 1Virna Margarita Martín Giménez Virna Margarita Martín Giménez 2Wenqing Xu Wenqing Xu 1Fiona Sailer Fiona Sailer 1Maike Windbergs Maike Windbergs 1Walter Manucha Walter Manucha 3Andreas Weigert Andreas Weigert 1*Ralf P Brandes Ralf P Brandes 1*
  • 1 Goethe University Frankfurt, Frankfurt, Germany
  • 2 Catholic University of Cuyo, San Juan, San Juan, Argentina
  • 3 Universidad Nacional de Cuyo, Mendoza, Mendoza, Argentina

The final, formatted version of the article will be published soon.

    Anandamide (AEA) is an endocannabinoid that has recently been recognized as a regulator of various inflammatory diseases as well as cancer. While AEA was thought to predominantly engage cannabinoid (CB) receptors, recent findings suggest that, given its protective anti-inflammatory role in pathological conditions, anandamide may engage not only CB receptors. In this study, we sought to understand the role of exogenous AEA in a mouse model of acute inflammation. We found that AEA decreases the acute infiltration of myeloid cells including granulocytes and monocytes into the inflamed area, but unexpectedly increases the number of T cells at the site of inflammation. This was related to AEA signaling through nuclear receptor subfamily 4A (NR4A) transcription factors rather than CB receptors.Exploring regulatory mechanisms in the human system, we found that AEA broadly inhibits the migratory capacity of immune cells arguing for blocked emigration of T cells from the inflamed tissue. Taking a closer look at the impact of AEA on T cells revealed that AEA profoundly alters the activation and exhaustion status of CD4+ T and CD8+ T cells, thereby strongly inhibiting TH17 responses, while not altering TH1 differentiation. These data suggest that AEA has the potential to block chronic inflammation without influencing crucial anti-viral and anti-microbial immune defense mechanisms, and may therefore be an attractive molecule to interfere with the establishment of chronic inflammation.

    Keywords: AEA, Endocannabinoids, T cells, Inflammation, Lipids

    Received: 15 Nov 2024; Accepted: 04 Dec 2024.

    Copyright: © 2024 Kiprina, Teichmann, Martín Giménez, Xu, Sailer, Windbergs, Manucha, Weigert and Brandes. 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) or licensor 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:
    Andreas Weigert, Goethe University Frankfurt, Frankfurt, Germany
    Ralf P Brandes, Goethe University Frankfurt, Frankfurt, Germany

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.