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Pro- and anti-inflammatory bioactive lipids imbalance contributes to the pathobiology of autoimmune diseases

European Journal of Clinical Nutrition volume 77, pages 637–651 (2023)Cite this article

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Abstract

Autoimmune diseases are driven by TH17 cells that secrete pro-inflammatory cytokines, especially IL-17. Under normal physiological conditions, autoreactive T cells are suppressed by TGF-β and IL-10 secreted by microglia and dendritic cells. When this balance is upset due to injury, infection and other causes, leukocyte recruitment and macrophage activation occurs resulting in secretion of pro-inflammatory IL-6, TNF-α, IL-17 and PGE2, LTs (leukotrienes) accompanied by a deficiency of anti-inflammatory LXA4, resolvins, protecting, and maresins. PGE2 facilitates TH1 cell differentiation and promotes immune-mediated inflammation through TH17 expansion. There is evidence to suggest that autoimmune diseases can be suppressed by anti-inflammatory bioactive lipids LXA4, resolvins, protecting, and maresins. These results imply that systemic and/or local application of LXA4, resolvins, protecting, and maresins and administration of their precursors AA/EPA/DHA could form a potential therapeutic approach in the prevention and treatment of autoimmune diseases.

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Fig. 1: A peripheral lymphocyte showing the presence of micronucleus (MN) (arrow) in its cytoplasm.
Fig. 2: cGAS-STING pathway in autoimmune process.
Fig. 3: Scheme showing EFA metabolism, interaction, and feedback regulation among immunocytes, cytokines, various bioactive lipids (BALs), and inflammation.
Fig. 4: Factors that have a regulatory role in the formation of different subsets of T helper cells.
Fig. 5: Scheme showing polarization of Naive CD+ T cells to Treg and TH17 cells and factors influencing this process.
Fig. 6: Lipoxin biosynthesis and structures.
Fig. 7: Effect of PGE1 and PGE2 on the generation of LXA4.
Fig. 8: Effect of various unsaturated fatty acids on the generation of LXA4 inhibited by streptozotocin (STZ)-treated RIN (rat inulinoma) cells in vitro.

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  1. UND Life Sciences, 2221 NW 5th St, Battle Ground, WA, 98604, USA

    Undurti N. Das

  2. Department of Biotechnology, Indian Institute of Technology-Hyderabad, Sangareddy, Telangana, 502284, India

    Undurti N. Das

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Das, U.N. Pro- and anti-inflammatory bioactive lipids imbalance contributes to the pathobiology of autoimmune diseases. Eur J Clin Nutr 77, 637–651 (2023). https://doi.org/10.1038/s41430-022-01173-8

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