Autoimmune conditions may affect up to 10% of the population, and genetic, lifestyle, epigenetic, and environmental factors dynamically impact risks for autoimmune issues. Autoimmunity involves the inappropriate generation of antibodies to components of the body at a systemic or organ-specific level, and can subsequently heighten risk for cancer and other diseases.

A common feature underlying autoimmunity is imbalanced activities or numbers of T-helper cell (Th cell) subsets combined with insufficient moderating influence from regulatory T cells (Tregs), which normally help preserve immune tolerance to ‘self’ immune markers. If this imbalance is not corrected, it can eventually result in overproduction of proinflammatory cytokines, activation of tissue enzymes, loss of self-tolerance, and the generation of autoantibodies. Activated T cells release chemical messengers that can expand or delimit adaptive as well as innate immune responses, including interleukins, interferons, cytokines, growth factors, and nuclear signaling factors (tumor necrosis factor, etc.).

Polyphenols are phytonutrients that are being studied for their influence at the innate/adaptive immune interface. Dietary polyphenols possess a considerable range of antioxidant potential, and additionally display beneficial antimicrobial, neuroprotective, metabolic, and cardiovascular properties. Those under research for immunomodulatory activity in autoimmunity include curcumin, quercetin, ginkgo flavonoids, epigallocatechin gallate (EGCG), apigenin, luteolin, resveratrol, hesperidin, anthocyanidins, fisetin, genistein, milk thistle flavonoids, and others. Their broad ability to downregulate the production of proinflammatory signaling molecules may aid balance among T-cell subsets, support intestinal integrity, and limit inappropriate generation of antibodies and destructive tissue enzymes.

This study examines the effects of polyphenols on signaling networks that control the initiation, expansion, and conclusion of the immune response. Specific messaging pathways examined include:

• The arachidonic acid pathway of eicosanoid lipid mediator metabolism (involving cyclooxygenases, lipoxygenases, and related enzymes)
• Epigenetic regulation of gene activation and silencing to alter the development and mobilization of immune cell lineages
• The nuclear factor-kappa B (NFκB) and mitogen-activated protein kinase (MAPK) systems influencing proinflammatory gene expression (for tumor necrosis factor, other cytokines, LOX, COX, etc.)
• The phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) pathways modulating cellular energy metabolism and cytokine expression