Immune and Metabolic Interactions of Human Erythrocytes: A Molecular Perspective

Abstract

Background: Apart from their main function as oxygen carriers in vertebrates, erythrocytes are also involved in immune regulation. By circulating throughout the body, the erythrocytes are exposed and interact with tissues that are damaged as a result of a disease. Methods: In this study, we summarize the literature regarding the contribution of erythrocytes to immune regulation and metabolism. Results: Under the circumstances of a disease state, the erythrocytes may lose their antioxidant capacity and release Damage Associated Molecular Patterns, resulting in regulation of innate and adaptive immunity. In addition, the erythrocytes scavenge and affect the levels of chemokines, circulating cell-free mtDNA and C3b attached immune complexes. Furthermore, through surface molecules, erythrocytes control the function of T lymphocytes, macrophages and dendritic cells. Through an array of enzymes, red blood cells contribute to the pool of blood’s bioactive lipids. Finally, the erythrocytes contribute to reverse cholesterol transport, through various mechanisms. Conclusion: Our study is highlighting overlooked molecular interactions between erythrocytes and immunity and metabolism, which could lead to the discovery of potent therapeutic targets for immunometabolic diseases.

Red Blood Cell-Conditioned Media from Non-Alcoholic Fatty Liver Disease Patients Contain Increased MCP1 and Induce TNF-α Release

“…Apart from their typical role as oxygen transporters, human erythrocytes retain a considerable immunomodulatory capacity (11,12). Interestingly, erythrocytes constitute important pools of cytokines, chemokines, S1P, LPA and Cholesterol in the blood (13).…”

Non-alcoholic steatohepatitis patients exhibit reduced CD47, and increased sphingosine, cholesterol and MCP1 levels in the erythrocyte membranes

“…This event leads to the formation of ceramide 31 , sphingosine, and release of microvesicles 32 . Interestingly, erythrocyte sphingolipid metabolism can result in the formation of sphingosine 1-phosphate (S1P) 9 , a bioactive lipid mediator, implicated in the pathogenesis of NASH 33 . It has previously been shown that erythrocyte membranes of NASH patients, contain decreased levels of sphingomyelin 34 , and that erythrocyte-conditioned media do not contain elevated S1P 14 .…”

“…Red blood cells are also important players of the reverse cholesterol transport 9 . Since, cholesterol accumulation contributes to the inflammatory process of NASH, we wondered whether erythrocyte membranes of NASH patients contain increased cholesterol levels.…”

“…Erythrocytes are important modulators of the adaptive and innate immunity, and participate in the systemic metabolism of lipids 9 . In addition, erythrocyte function is heavily influenced by toxic lipid mediators 10 , hormones 11 and molecular constituents of inflammation, all important hallmarks of NASH pathogenesis 12 .…”

Ανοσοβιολογική Μελέτη Της Εμπλοκής Των Ερυθροκυττάρων Στους Παθογενετικούς Μηχανισμούς Της Μη Αλκοολικής Ηπατικής Νόσου

“…Αξίζει να σημειωθεί ότι τα ερυθρά αιμοσφαίρια είναι ένας τύπος κυττάρου του οποίου ο ρόλος στη ρύθμιση της ανοσολογικής λειτουργίας 409 , και τον μεταβολισμό και την διακίνηση λιπιδίων δεν έχει πλήρως εκτιμηθεί 410 . Η δίαιτα με υψηλή περιεκτικότητα σε λιπαρά προκαλεί αύξηση της χοληστερόλης της μεμβράνης ερυθροκυττάρων 411 , ενώ η γήρανση των ερυθροκυττάρων σχετίζεται με τη συσσώρευση οξειδωμένων φωσφολιπιδίων in vivo 412 .…”