Blocking Microglial Proliferation by CSF-1R Inhibitor Does Not Alter the Neuroprotective Effects of Adoptive Regulatory T Cells in 3xTg Alzheimer’s Disease Mice

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript "Blocking microglial proliferation by CSF-1R inhibitor does not 
alter the neuroprotective effects of adoptive regulatory T cells in 3xTg Alzheimer's disease mice" by Park et al., proposed to investigate protective role of adoptive Tregs therapy in supressing microglia mediation neuroinflammation in 3xTg AD model. Authors have presented the finding well with the required sets of experiments. I have following comments for authors to consider to further improve the quality of the manuscript. 

1. The figure legends looks short and needs to to expanded with more details. 

2. Material and Methods; what coordinates of brain were used for sectioning? Does whole brain was used for the RNA extraction?

3. Figure 5, please increase the font size for all the graphs to make it more readable. 

4. Discussion needs to be expanded to include more current findings with Adoptive Treg therapy with respect to AD and other neuroinflammatory diseases. 

5. Schematic summering the key findings would attract more readers for the paper. 

Comments on the Quality of English Language

None

Author Response

First of all, thank you for your interest in our paper, entitled on ‘Blocking microglial proliferation by CSF-1R inhibitor does not alter the neuroprotective effects of adoptive regulatory T cells in 3xTg Alzheimer's disease mice’ to Current Issues in Molecular Biology. We also appreciate the time and consideration you have for our paper. Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Overview of the manuscript
The article focuses on studying the neuroprotective effects of adoptive regulatory T cells in a mice model of Alzheimer disease. The authors want to evaluate that, during inhibitory protocol of microglial proliferation, the use of adoptive regulatory T cells remains useful in suppressing the microglial activation and Tregs remain in place for long time. The authors using molecular, morphological and behavioural methodologies, effectively found that adoptively transferred Tregs can survive more than 100 days in the brain, alleviating AD pathology. The authors conclude on the efficacy of adoptive Treg therapy in AD.  

   

GENERAL COMMENT

The work is interesting in underlining the importance and effectiveness of adoptive Treg therapy in AD in association with the microglial inhibition protocol, which is currently a widely used protocol to reduce the inflammatory pattern generate by reactive microglial. The experimental plan is appropriate and consistent with the aims of the work. The methodologies adopted are consistent and provide adequate support for the authors’ conclusions.

However, the topic of the work should be better presented in abstract and introduction section. Because the association between the exploration on the anti-inflammatory action of Treg and a contemporaneous microglial inhibitory protocol is not immediately understandable.

 

 SPECIFIC COMMENTS

Abstract

The abstract should be revised to better explain the use of the microglial inhibitory protocol in exploring the anti-inflammatory role of Treg.

Pag. 1, line 16: CSF-1R deplete or inhibit the microglial cells? Explain better.

Pag. 1, line 20: GW 2580, it should be named before

Introduction

The introduction section should be revised to better explain the focus of the use of microglial inhibitory protocol in exploring the anti-inflammatory role of Treg.

Pag. 2, line 56: which is the importance of exploratory presence of Treg in other tissue? Which tissue? Explain better.

Results

Fig. 6: The meaning of the several arrows drawing is unclear. What do they mean to indicate? Explain better in legend.

 Discussion

Pag. 10, line 304-306: the sentence is unclear. Rewrite it and explain better.

Author Response

First of all, thank you for your interest in our paper, entitled on ‘Blocking microglial proliferation by CSF-1R inhibitor does not alter the neuroprotective effects of adoptive regulatory T cells in 3xTg Alzheimer's disease mice’ to Current Issues in Molecular Biology. We also appreciate the time and consideration you have for our paper. Please see the attachment.

Author Response File: Author Response.pdf