Pro-Resolving Lipid Mediators Are Critical in Modulating T-Cell Responses

A recent paper established that adaptive immune responses in human peripheral blood lymphocytes were in part modulated by resolvins and maresins, molecules produced in the body naturally from certain omega-3 fatty acids.

Resolvins are autacoids (biological factors which act like local hormones, have a brief duration, and act near the site of synthesis) of a specific lipid structure: dihydroxy or trihydroxy metabolites of omega-3 fatty acids, primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) but also the docosapentaenoic acid (DPA), clupanodonic acid. They are members of an expanding class of polyunsaturated fatty acid (PUFA) metabolites termed specialized pro-resolving mediators (SPMs). Other SPMs include the lipoxins, protectin D1 and its related products, and the maresins.

SPMs possess potent anti-inflammation, tissue protection, and tissue healing activities in diverse animal models and accordingly are proposed to be involved in resolving physiological inflammatory responses. Their failure to form in adequate amounts is also proposed to underlie a broad range of human diseases involving pathological inflammation.

As the resolution of inflammation is a finely regulated process mediated by specialized SPMs, their immunomodulatory role in adaptive immune cells is of considerable interest. In exploring this role, investigators at Brigham and Women's Hospital (Boston, MA, USA) found that D-series resolvins (resolvin D1 and resolvin D2) and maresin 1 modulated adaptive immune responses in human peripheral blood lymphocytes. These lipid mediators reduced cytokine production by activated CD8+ T-cells and CD4+ T helper 1 (TH1) and TH17 cells but did not modulate T-cell inhibitory receptors or abrogate their capacity to proliferate. Moreover, these SPMs prevented naïve CD4+ T cell differentiation into TH1 and TH17 by down-regulating their signature transcription factors.

The investigators also reported in the August 24, 2016, online edition of the journal Science Translational Medicine that a mouse model that was unable to generate precursors for these lipid mediators had an increase of TH1 and TH17 cells and relatively fewer regulatory T-cells than wild-type mice.

"It is now widely appreciated that uncontrolled inflammation is integral to many human diseases including neurodegenerative diseases, cardiovascular diseases as well as chronic inflammatory disease," said senior author Dr. Charles N. Serhan, director of the center for experimental therapeutics and reperfusion injury at Brigham and Women's Hospital. "The results of this study now provide the ground work to appreciate the role of resolvins, and potentially other novel pro-resolving mediators, in the immune system. Armed with the results of this collaboration, we and other investigators can now consider new treatments and therapeutic strategies for translating these findings with pro-resolving mediators to human health and many diseases."

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