Insights into CD24 and Exosome Physiology and Potential Role in View of Recent Advances in COVID-19 Therapeutics: A Narrative Review

Abstract

Cluster of differentiation (CD) 24, a long-known protein with multifaceted functions, has gained attention as a possible treatment for Coronavirus Disease 19 (COVID-19) due to its known anti-inflammatory action. Extracellular vesicles (EVs), such as exosomes and microvesicles, may serve as candidate drug delivery platforms for novel therapeutic approaches in COVID-19 and various other diseases due to their unique characteristics. In the current review, we describe the physiology of CD24 and EVs and try to elucidate their role, both independently and as a combination, in COVID-19 therapeutics. CD24 may act as an important immune regulator in diseases with complex physiologies characterized by excessive inflammation. Very recent data outline a possible therapeutic role not only in COVID-19 but also in other similar disease states, e.g., acute respiratory distress syndrome (ARDS) and sepsis where immune dysregulation plays a key pathophysiologic role. On the other hand, CD24, as well as other therapeutic molecules, can be administered with the use of exosomes, exploiting their unique characteristics to create a novel drug delivery platform as outlined in recent clinical efforts. The implications for human therapeutics in general are huge with regard to pharmacodynamics, pharmacokinetics, safety, and efficacy that will be further elucidated in future randomized controlled trials (RCTs).

Keywords: CD24; COVID-19; exosomes.

Figure 1

Toll-like receptors (TLRs) on the surface of immune cells, recognize pathogen-associated molecular patterns (PAMPs) or components of injured cells, referred to as damage-associated molecular patterns (DAMPs). TLR metabolic pathway leads to upregulation of nuclear factor-κΒ (NF-κΒ) and proinflammatory cytokine production. Inhibition of NF-κB pathway and consequent cytokine storm, seems to be a promising therapeutic strategy against deterioration of patients with moderate to severe COVID-19.

Figure 2

Exosomes carrying CD24, named EXO-CD24, combine advantages of both exosomes as a novel drug delivery platform and CD24 as a potent immune checkpoint surveillance molecule. CD24 interacts with both DAMPs and Siglec 10. CD24’s link to DAMPs prevents them from binding to the TLRs, therefore inhibiting the NF-ĸB pathway that induces the production of cytokines and chemokines. At the same time, the CD24-Siglec 10 axis negatively regulates the activity of NF-ĸB through ITIM domains associated with SHP-1. While CD24 interacts with DAMPs and Siglec 10, it does not affect immune recognition through PAMPs, thereby allowing the innate immune response to achieve viral clearance. CD24, Cluster of differentiation 24; DAMPs, damage-associated molecular patterns; ITIM, immunoreceptor tyrosine-based inhibition motif; NF-κΒ, nuclear factor-κΒ; PAMPs, pathogen-associated molecular patterns; Siglec 10, sialic acid binding immunoglobulin-like lectin 10; SHP-1, SRC homology 2-domain-containing protein tyrosine phosphatase 1; TLR, Toll-like receptor. Created with BioRender.com (accessed on 7 September 2022).