Promising use of immune cell‐derived exosomes in the treatment of SARS‐CoV‐2 infections

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is persistently threatening the lives of thousands of individuals globally. It triggers pulmonary oedema, driving to dyspnoea and lung failure. Viral infectivity of coronavirus disease 2019 (COVID‐19) is a genuine challenge due to the mutagenic genome and mysterious immune‐pathophysiology. Early reports highlighted that extracellular vesicles (exosomes, Exos) work to enhance COVID‐19 progression by mediating viral transmission, replication and mutations. Furthermore, recent studies revealed that Exos derived from immune cells play an essential role in the promotion of immune cell exhaustion by transferring regulatory lncRNAs and miRNAs from exhausted cells to the active cells. Fortunately, there are great chances to modulate the immune functions of Exos towards a sustained repression of COVID‐19. Engineered Exos hold promising immunotherapeutic opportunities for remodelling cytotoxic T cells’ function. Immune cell‐derived Exos may trigger a stable epigenetic repression of viral infectivity, restore functional cytokine‐producing T cells and rebalance immune response in severe infections by inducing functional T regulatory cells (Tregs). This review introduces a view on the current outcomes of immunopathology, and immunotherapeutic applications of immune cell‐derived Exos in COVID‐19, besides new perspectives to develop novel patterns of engineered Exos triggering novel anti‐SARS‐CoV‐2 immune responses.

Immune cells‐derived exosomes: A promising strategy for COVID‐19 treatment

“…At present, there are a lot of researches and reviews on Exos and extracellular vesicles against COVID‐19, while most of them focus on the role and possibility of treatment in specific sources, 2,5–7 without the whole research progress in the era of COVID‐19 outbreak 8 . A recent review published in Clinical and Translational Medicine presents important insights into current immunopathology and the applications of immune cell‐derived Exos for the immunotherapy of COVID‐19 9 . Exos derived from immune cells could trigger novel anti‐SARS‐CoV‐2 immune responses, which are effective in reducing the inflammatory response.…”

“…Compared to antibody therapy and small molecule, the ability to home at its origin tissue, cell processes control through mediating multifunction and simple differentiation and labeling give Exos numerous advantages in the treatment of COVID‐19 9 . While there is no definite theoretical basis for the immune modulation mechanisms driven by Exos, especially corresponding dynamic structure alterations involved in the interactions among Exos, virions, and host cells.…”

“… 8 A recent review published in Clinical and Translational Medicine presents important insights into current immunopathology and the applications of immune cell‐derived Exos for the immunotherapy of COVID‐19. 9 Exos derived from immune cells could trigger novel anti‐SARS‐CoV‐2 immune responses, which are effective in reducing the inflammatory response. In addition, Exos inhibits the proliferation and activity of T helper cell 17 (Th17), which plays an important role in inducing respiratory failure through the delivery of regulatory miRNAs.…”

“…18 Compared to antibody therapy and small molecule, the ability to home at its origin tissue, cell processes control through mediating multifunction and simple differentiation and labeling give Exos numerous advantages in the treatment of COVID-19. 9 While there is no definite theoretical basis for the immune modulation mechanisms driven by Exos, especially corresponding dynamic structure alterations involved in the interactions among Exos, virions, and host cells. With the development of super-resolution microscopy (SRM), fluorescence images of the interaction between Exos and SARS-CoV-2 beyond the diffraction limit have been possible, and the detailed structures related to Exos can be benefited from cryo-electron microscopy (cryo-EM).…”

T cell-derived exosomes in tumor immune modulation and immunotherapy

“…Intercellular communication is an essential hallmark of multicellular organisms and can be mediated through direct cell-cell contact or the transfer of secreted molecules (9). Increasing studies have shown that immune cells participate in cellular communication by secreting exosomes (10,11). Among the immune cell-derived exosomes, T cell-derived exosomes have recently been reported to be involved in antitumor effects in cancer immunotherapy by mimicking the role of parental cells (12)(13)(14)(15).…”