Lipid‐based regulators of immunity

Abstract

Lipids constitute a diverse class of molecular regulators with ubiquitous physiological roles in sustaining life. These carbon‐rich compounds are primarily sourced from exogenous sources and may be used directly as structural cellular building blocks or as a substrate for generating signaling mediators to regulate cell behavior. In both of these roles, lipids play a key role in both immune activation and suppression, leading to inflammation and resolution, respectively. The simple yet elegant structural properties of lipids encompassing size, hydrophobicity, and molecular weight enable unique biodistribution profiles that facilitate preferential accumulation in target tissues to modulate relevant immune cell subsets. Thus, the structural and functional properties of lipids can be leveraged to generate new materials as pharmacological agents for potently modulating the immune system. Here, we discuss the properties of three classes of lipids: polyunsaturated fatty acids, short‐chain fatty acids, and lipid adjuvants. We describe their immunoregulatory functions in modulating disease pathogenesis in preclinical models and in human clinical trials. We conclude with an outlook on harnessing the diverse and potent immune modulating properties of lipids for immunoregulation.

Lipid Nanoparticle with 1,2-Di-O-octadecenyl-3-trimethylammonium-propane as a Component Lipid Confers Potent Responses of Th1 Cells and Antibody against Vaccine Antigen

“…Several reports indicate that some TLR-mediated pathways are important driving forces of Th1-type responses. − Therefore, these results suggest that the adjuvant mechanism of DOTMA50-LNP differs from that of other LNP adjuvants and may be mediated by pattern recognition receptors (PRRs) other than TLR4 and NLRP3. As one of the mechanisms of lipid immune activation, certain lipopeptides have been shown to act as agonists for TLR2 and activate immune cells. − Recent studies have reported that lipids are recognized by the C-type lectin receptor, one of the PRRs, and activate innate and adaptive immunity. , Additionally, several studies have indicated that certain lipids can modulate the activity of immune cells by acting as ligands for G-protein-coupled receptors. , Although several reports indicate the involvement of lipids in immune activation, it remains unclear whether stimulation of such pathways induces Th1 cells, making it challenging to precisely determine the mechanism by which DOTMA50-LNPs induce robust immunity.…”

Altered intestinal microbiota enhances adenoid hypertrophy by disrupting the immune balance

“…The expansion of the Th2 subset may be due to the drastic reduction of Treg cells systemically and locally. Previous studies found that SCFAs produced by gut microbiota are important immunomodulators that increase the expression of the transcription factor FOXP3 via inhibition of histone deacetylation to induce the differentiation of Treg cells ( 83 – 85 ). Eubacterium hallii , Oscillospira and Akkermansia in the gut are involved in the production of SCFAs, primarily acetate, propionate, and butyrate.…”

Investigation of the In Vitro Immunomodulatory Effects of Extracts from Green-Lipped Mussels (Perna canaliculus)

“…Omega-3 polyunsaturated fatty acids (PUFAs), such as a-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), have been studied for their regulatory impact on immune function [20,21]. Omega-3 competes with omega-6 fatty acids in enzymatic processes, affecting immune cell activities, integrating into cell membranes, influencing signalling, gene expression, lipid mediator production, and playing a role in gene transcription and lipid metabolism, thereby offering insights into immune modulation [22,23]. This lipid modification plays a crucial role in the functions of both innate and adaptive immune cells by affecting membrane composition, fluidity, and receptor interactions.…”