RhoA- and Actin-Dependent Functions of Macrophages from the Rodent Cardiac Transplantation Model Perspective -Timing Is the Essence

Round 1

Reviewer 1 Report

Review:

 

This is a primarily a review article summarising in general the role of the GTPase Rho in cellular mechanics and functioning in relation to the immune system, and cellular actin. The authors then provide a synopsis of their research in cardiac transplantation – and the potential role of Rho in regulating chronic rejection. It is well written. There is no data reporting.

 

There are several comments for the authors to address: They provide several paragraphs that in brief summarise the Rho role in Macrophage function, phagocytosis, receptor recycling, tunnelling nanotubles, intracellular actin filaments and cell locomotion, and extracellular matrix degredation. Each section flows well on from the other – however inclusion of a subsection on nuclear actin  - without any link to Rho or chronic rejection makes this section questionable for its inclusion in the article. Reason for inclusion should explained and how the authors see nuclear actin being relevant in relation to the aim of the article – especially in cardiac transplantation.

 

Further diagrams for each section explaining the complicated intercellular processes in more graphical format should be included to aid reader understanding.

 

The final sections of the article describes the authors research in murine cardiac transplantation and their aims/goals in relation to use of Rho as a molecular target to limit chronic rejection.

 

As per the title of the article the final paragraphs relate to the temporal nuances of chronic rejection and how therapeutic interventions could be developed. This approach is not novel but is not widely considered – and explanation to readers would be improved with several diagrams. Furthermore the authors allude to circadian effects on rejection in the final few paragraphes of the article – this is novel topic however should be placed in context of current treatments, and in relation to the authors expertise – murine cardiac transplantation rejection models. This section should be expanded upon.

 

There is no conclusion as such in the article. The final part should indicate to the readers how the authors propose progress in the next steps of research into the field should be, and reference any other groups that are working on such approaches.

 

Author Response

Reviewer 1:

 This is a primarily a review article summarising in general the role of the GTPase Rho in cellular mechanics and functioning in relation to the immune system, and cellular actin. The authors then provide a synopsis of their research in cardiac transplantation – and the potential role of Rho in regulating chronic rejection. It is well written. There is no data reporting.

 There are several comments for the authors to address: They provide several paragraphs that in brief summarise the Rho role in Macrophage function, phagocytosis, receptor recycling, tunnelling nanotubles, intracellular actin filaments and cell locomotion, and extracellular matrix degredation. Each section flows well on from the other – however inclusion of a subsection on nuclear actin  - without any link to Rho or chronic rejection makes this section questionable for its inclusion in the article. Reason for inclusion should explained and how the authors see nuclear actin being relevant in relation to the aim of the article – especially in cardiac transplantation.

RESPONSE: We would like to keep the nuclear actin section-this is a very important but rearly covered subject, but as the reviewer suggested we added the paragraph explaining the relevance and the connection of nuclear actin to the transplantation and other subjects of the article.

 Further diagrams for each section explaining the complicated intercellular processes in more graphical format should be included to aid reader understanding.

RESPONSE: As requested we added the diagrams: TNT formation, Transplant rejection time line, and Podosome diagram

 The final sections of the article describes the authors research in murine cardiac transplantation and their aims/goals in relation to use of Rho as a molecular target to limit chronic rejection.

 As per the title of the article the final paragraphs relate to the temporal nuances of chronic rejection and how therapeutic interventions could be developed. This approach is not novel but is not widely considered – and explanation to readers would be improved with several diagrams.

RESPONSE: as requested we added the diagram

Furthermore the authors allude to circadian effects on rejection in the final few paragraphes of the article – this is novel topic however should be placed in context of current treatments, and in relation to the authors expertise – murine cardiac transplantation rejection models. This section should be expanded upon.

RESPONSE: As requested we expanded this section asnd added reference

 There is no conclusion as such in the article. The final part should indicate to the readers how the authors propose progress in the next steps of research into the field should be, and reference any other groups that are working on such approaches.

RESPONSE: As requested we added the conclusions and proposed next steps and approaches

 

 

 

Reviewer 2 Report

In summary, this is a clear, succinct, and well-written review article. Adequate information about the previous findings has been presented for the readers to follow up this review article. However, the authors have already written multiple review articles on similar topics, I do not particularly find anything exciting about this review article. If the authors are going to publish this review, then I think a nice addition to the topic would be crosstalk or mutual regulation of actin and microtubule cytoskeleton in immune cells and transplant rejections.

Author Response

Reviewer 2

In summary, this is a clear, succinct, and well-written review article. Adequate information about the previous findings has been presented for the readers to follow up this review article. However, the authors have already written multiple review articles on similar topics, I do not particularly find anything exciting about this review article. If the authors are going to publish this review, then I think a nice addition to the topic would be crosstalk or mutual regulation of actin and microtubule cytoskeleton in immune cells and transplant rejections.

RESPONSE: As requested we added the paragraph on the crosstalk between actin and microtubule cytoskeleton in immune cells and transplant rejections.

 

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Comments acted upon and changes made. No further suggestions.