Palmitoylethanolamide (PEA) Induces an Increase in Spleen Regulatory T Cells, Reduces CD8+ Cells and TNF-α Levels in Target Organs, and Protects Mice From Graft-Versus-Host Disease-Related Mortality Through PPAR Activation Without Compromising the Graft-Versus-Tumour Response.
Bárbara Betônico Berg, Zara Desiree Tonidandel Campos, Gioconda Muniz Fiorenza Ruggio, Ana Flávia Santos Linhares, Bárbara Maximino Rezende, Stêfany Bruno de Assis Cau, Thiago Roberto Lima Romero, Mauro Martins Teixeira, Vanessa Pinho, Marina Gomes Miranda Castor
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引用次数: 0
Abstract
Graft-versus-host disease (GVHD), a secondary complication of bone marrow transplantation, leads to the development of a systemic inflammatory illness in the host, resulting in high mortality and morbidity. Current therapies lack prophylactic effectiveness and often fail to achieve an optimal immunological balance between inflammation and immunosuppression. In this study, we investigated the effects of palmitoylethanolamide (PEA), an endocannabinoid-like lipid mediator with extensively documented anti-inflammatory, analgesic, antimicrobial, immunomodulatory, and neuroprotective effects, on the complex pathology of GVHD. Treatment with PEA reduced clinical disease severity in GVHD mice, leading to an 80% increase in survival rates. Additionally, PEA created an immunoregulatory environment in the spleen by reducing the activation of CD3+CD4+ cells. In the intestine, PEA protected against damage, reduced the number of CD3+CD4+ and CD3+CD8+ cells, and suppressed the activation of CD3+CD8+ cells. PEA also decreased the levels of TNF-α in the intestine and increased IL-10 production. Furthermore, in the liver, PEA treatment reduced the number of CD8+ cells, the activation of CD3+CD4+ and CD3+CD8+ cells, and TNF-α levels. The effect of PEA on survival was dependent on Peroxisome Proliferator-activated receptor gamma (PPAR-γ) activation but did not rely on cannabinoid (CB) receptors activation. In addition to GVHD protection, PEA treatment did not interfere in the graft-versus-tumour response. These results demonstrate the therapeutic potential of PEA as a promising option for the treatment of GVHD, balancing inflammation and immunosuppression, and improving both survival and clinical outcomes.
期刊介绍:
Immunology is one of the longest-established immunology journals and is recognised as one of the leading journals in its field. We have global representation in authors, editors and reviewers.
Immunology publishes papers describing original findings in all areas of cellular and molecular immunology. High-quality original articles describing mechanistic insights into fundamental aspects of the immune system are welcome. Topics of interest to the journal include: immune cell development, cancer immunology, systems immunology/omics and informatics, inflammation, immunometabolism, immunology of infection, microbiota and immunity, mucosal immunology, and neuroimmunology.
The journal also publishes commissioned review articles on subjects of topical interest to immunologists, and commissions in-depth review series: themed sets of review articles which take a 360° view of select topics at the heart of immunological research.