Ex Vivo-Generated Tolerogenic Dendritic Cells: Hope for a Definitive Therapy of Autoimmune Diseases

Round 1

Reviewer 1 Report

This review addresses the description of tolerogenic DCs, methods of their induction, and the use of DC immunotherapy for autoimmune diseases. The review reads with great interest and creates a fairly complete picture of the potential clinical applications of DC-mediated immunotechnologies.

My comments and suggestions.

1. The abstract has little information. The abstract should include the key postulates that highlight the raised topic.

2. A reference is required for the statement in the text “In addition, studies show that DC has a central role in maintaining a balance of central or peripheral tolerance (lines 78-79)”.

3. The inadequate cell apoptosis in systemic lupus erythematosus triggers the production of particular antinuclear antibodies, which may serve as a protective mechanism to enhance the uptake (phagocytosis) of undegraded nucleic acids in biological fluids. If so, tolerance induction aimed at inhibiting the production of antinuclear antibodies could exacerbate the disease. That would be interesting to discuss. 

Author Response

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Author Response File: Author Response.pdf

Reviewer 2 Report

In the current review, the authors discussed the dendritic cell’s role in the pathogenesis of systemic lupus erythematosus and how to use DC in other autoimmune disease therapy instead of immunosuppressive drugs. The review is well-written. The flow of ideas is organized. The problems and challenges of DC immunotherapy are also explained in this review.  The majority of the references are not recent, but they are acceptable. However, this review does not state suggested solutions for DC immunotherapy, so it must be clarified. Only some suggestions were addressed, as listed below:

1. The introduction should clearly state this review's unique features and purpose, highlighting the gaps in other similar reviews.
2. In the introduction, the authors stated “In recent years, researchers have developed approaches to ex vivo differentiation…" However, the reference is from 2013!
3. The conclusion section must be improved.

Author Response

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Author Response File: Author Response.pdf

Reviewer 3 Report

This review aims to explore the role of dendritic cells (DCs) in the pathogenesis of autoimmune diseases, specifically focusing on their therapies for systemic lupus erythematosus (SLE). Despite the title suggesting a hope for SLE, readers may find the discussion largely on general autoimmune diseases, with abrupt introduction of SLE in some sections. Additionally, the article doesn’t include recent advancements in the tolDCs mediated SLE therapies. Several other previously published reviews 10.1016/j.jaut.2022.102856; 10.1016/j.autrev.2014.10.010; 10.12932/AP-070919-0639; j.intimp.2022.109601; have already discussed the role of DCs in both autoimmune diseases and SLE. Section 1 and Section 2 are clearly discussed in the article. However, section 3, which is important in the article is very poorly discussed. There are not many studies discussed and the studies discussed lack a detailed explanation and discussion. It would be beneficial for the authors to present all types of treatments in a single figure, illustrating different strategies. Authors need to change the title, rewrite the abstract and introduction, restructure the review and enhance the quality of presentation for a more comprehensive understanding.

Author Response

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Author Response File: Author Response.pdf

Round 2

Reviewer 3 Report

Authors made changes to the article. However, the modifications do not provide necessary changes as mentioned in the previous review report. Authors were suggested to completely restructure the review and clearly discuss their intentions and suggestions. Other reviews have previously discussed what authors have suggested. 

Author Response

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Author Response File: Author Response.pdf

Round 3

Reviewer 3 Report

Authors made necessary changes as suggested and therefore suitable for publication