Cholesterol, inflammation and immunity

Cholesterol metabolism and immune response are closely linked. Cholesterol is critical for the synthesis of lipid rafts, which activate receptors involved in antigen recognition, influences the production of NET and modulates the activation and polarization of macrophages. Oxysterols in turn regulate macrophage activation, migration, and cytokine production. While the immune response modulates the expression of genes involved in the synthesis, absorption and efflux of cholesterol. Cholesterol accumulation in immune cells promotes proinflammatory immune responses creating a vicious cycle that sustains immune inflammation. High-density lipoproteins (HDL) are typically reduced during inflammation, when reverse cholesterol transport is impaired, thus promoting hyperactivation of TLR2 and TLR4 by lipopolysaccharide (LPS) and other microbial products, resulting in inhibition of stress-induced activating transcription (ATF) 3 and enhanced production of cytokines by macrophages. Further endangering an already delicate balance, HDL proinflammatory subfractions with lower content of apoA-1, antioxidant enzymes, and L-CAT, are produced, and further fuel inflammation.

Alterations in the biochemical network between cholesterol, inflammation and immunity are emerging as a pathogenetic mechanism of numerous human disorders, among which atherosclerosis, cardiovascular diseases and their complications, metabolic diseases and diabetes, infectious diseases and sepsis, autoimmune and auto-multiinflammatory disorders, acquired and congenital hypo-immune diseases, and cancer. Further deepening the knowledge of the mechanisms that impair the relationship between cholesterol, inflammation and immunity can have two translational impacts, i.e., i) the identification of novel biomarkers of these diseases; ii) define potential innovative therapies. While special issue aims to collect contributions related to the knowledge of the interactions between cholesterol metabolism, inflammation and the immune system in the pathogenesis of human diseases, we also encourage submission of articles aimed to the discovery of new biomarkers, potentially useful in the monitoring, diagnosis and therapy of human diseases, and studies on cellular or animal models describing preclinical approaches of potential targeted therapeutics.

This special issue aims to collect Original Research, Review, Mini Review, and Perspective articles (purely bioinformatics studies without experimental validation are not in scope for this section) on themes including: i) the better knowledge of the interactions between cholesterol metabolism, inflammation and the immune system in the pathogenesis of human diseases; ii) the discovery of novel diagnostic biomarkers; iii) preclinical approaches of potential targeted therapeutics. The themes will include, but are not limited to:

- Atherosclerosis and cardiovascular disease
- Multi-inflammatory diseases
- Auto-inflammatory diseases
- Infectious diseases and sepsis
- Autoimmune diseases
- Neurodegenerative diseases
- Biomarkers for diagnosis and monitoring
- Therapeutic target
- Preclinical models