Bioactive lipids ALIAmides differentially modulate inflammatory responses of distinct subsets of primary human T lymphocytes

Valerio Chiurchiù, Alessandro Leuti, Reem Smoum, Raphael Mechoulam, Mauro Maccarrone

Research output: Contribution to journalArticle

Abstract

Autacoid local injury antagonist amides (ALIAmides) are a family of endogenous bioactive acyl etha-nolamides that include the renowned palmitoyl ethanolamide (PEA), oleoyl ethanolamide (OEA), and stearoyl ethanolamide (SEA), and that are involved in several biologic processes such as nociception, lipid metabolism, and inflammation. The role of ALIAmides in the control of inflammatory processes has recently gained much attention and prompted the use of these molecules or their analogs, and the pharmacologic manipulation of their endogenous levels, as plausible therapeutic strategies in the treatment of several chronic inflammatory conditions. Since chronic inflammation is mainly driven by cells of adaptive immunity, particularly T lymphocytes, we aimed at investigating whether such bioactive lipids could directly modulate T-cell responses. We found that OEA, PEA, and eicosatrienoyl ethanolamide (ETEA) could directly inhibit both T-cell responses by reducing their production of TNF-a and IFN-g from CD8 T cells and TNF-a, IFN-g and IL-17 from CD4 T cells. Furthermore, neither SEA nor docosatrienoyl ethanolamide (DTEA) could affect cytokine production from both T cell subsets. Interestingly, unlike OEA and ETEA, PEA was also able to enhance de novo generation of forkhead box P3 (FoxP3)–expressing regulatory T cells from CD4-naive T cells. Our findings show for the first time that specific ALIAmides can directly affect different T-cell subsets, and provide proof of their anti-inflammatory role in chronic inflammation, ultimately suggesting that these bioactive lipids could offer novel tools for the management of T-cell dependent chronic inflammatory diseases.

Original languageEnglish
Pages (from-to)5716-5723
Number of pages8
JournalFASEB Journal
Volume32
Issue number10
DOIs
Publication statusPublished - Oct 1 2018

Fingerprint

Autacoids
T-cells
Amides
T-Lymphocytes
Lipids
Wounds and Injuries
T-Lymphocyte Subsets
Inflammation
Nociception
Interleukin-17
Adaptive Immunity
Regulatory T-Lymphocytes
Lipid Metabolism
Chronic Disease
Anti-Inflammatory Agents
Cytokines

Keywords

  • Adaptive immunity
  • Cytokines
  • N-acyl ethanolamines
  • T cells

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Bioactive lipids ALIAmides differentially modulate inflammatory responses of distinct subsets of primary human T lymphocytes. / Chiurchiù, Valerio; Leuti, Alessandro; Smoum, Reem; Mechoulam, Raphael; Maccarrone, Mauro.

In: FASEB Journal, Vol. 32, No. 10, 01.10.2018, p. 5716-5723.

Research output: Contribution to journalArticle

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