PREreview of Platelet-derived transcription factors license human monocyte inflammation

Review of: Platelets supply p38 MAPK signaling that licenses pro-inflammatory

cytokine responses of human monocytes

BioRxiv. DOI: https://doi.org/10.1101/2022.08.10.503291 

This preview was written by Chau Chiu Wang, a trainee in the Rio Sugimura lab at the University of Hong Kong as a part of his MBBS Enrichment Year Program.

Summary

Hawwari et al. investigated the role of platelet in the pro-inflammatory cytokine response of monocytes. They demonstrated that platelets supply p38 MAPK signal molecules to monocytes through direct contact. Depletion of platelets shut down pro-inflammatory genes while transfer platelets reactivated monocytes. This work provides insight into immunoparalysis in thrombocytopenia patients and the novel role of platelets to activate the innate immune reaction. 

The study revealed that platelets donate MAPK and transcription factors to monocytes. The successful activation of monocytes in the immunoparalysis state of ITP patients with platelet transfusion is clinically significant. This will reinforce the use of platelets as living-drug to target immune deficiency, autoimmunity, and cancers.

Major comments 

Strengths:

The study has the following strengths

1. The novel mechanism of platelet-mediated inflammation. The study could also shed light on previous studies on platelets and their role in regulating innate immune reactions to supply detailed mechanisms.

2. In vivo murine model and human cell lines were used to validate the claim in an orthogonal way. The experiments were well designed and demonstrated that platelet depletion impaired cytokine secretion by monocyte and can be rescued by platelet supplements.

3. This study uses a wide range of technologies to confirm the findings including FACS, RNA seq, confocal imaging, immunoblotting, and kinase microarray in addition to an orthogonal approach to the hypothesis, increasing the validity of the study. 

To be improved: 

What could be a mechanism of platelets donating monocytes MAPK and transcription factors? Direct contact, but phagocytosis, was suggested. Recent studies support tunneling membrane nanotubes in the interaction between immune cells and stromal cells. Might be intriguing to check in platelet–monocyte interactions. 

To further characterize the interaction of platelets with monocytes, I would suggest using calcium indicators for evidence of platelet degranulation or immunostaining of transcription factors.

Overall: 

To summarize, the authors did a thorough study exploring the effect of a platelet on monocyte activation. Their work could contribute to the foundation of developing a treatment for inflammatory diseases like atherosclerosis and thrombo-inflammation in COVID-19 by using platelets as living drugs. Besides clinical implications, the study also adds new knowledge to platelet-mediated monocyte activation and may help to perfect in vitro monocyte models.