Pro-Dermcidin as an Emerging Regulator of Innate Immunity in Sepsis
and Haichao Wang 1,2,*
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe manuscript, titled "Pro-dermcidin as an emerging regulator of innate immunity in sepsis", explores the immunomodulatory role of the precursor antimicrobial peptide pro-dermcidin (pro-DCD) in sepsis. The article has reasonable structure, clear logic and detailed data, which has high scientific value and potential clinical significance. However, there are also some areas for improvement, and here are the review comments on the article.
- To explore the specific mechanism of action of pro-DCD in sepsis, including how it regulates the immune response and promotes bacterial clearance. Propose new hypotheses and research directions. For example, innate immune signaling pathways TLR and STING (Reference: 1. José E Belizário. "Role of skin antimicrobial peptides in the pathogenesis of psoriasis, atopic dermatitis and hidradenitis suppurative: Highlights on dermcidin." Clinical Immunology Communications (2025); 2. PMID: 39939798 DOI: 10.1038/s41418-025-01457-z(2025)).
- References: Some of the cited references is relatively old, and it is suggested to supplement the important research progress in related fields in recent years to enhance the timeliness and persuasiveness of the articles.
- Conclusion should be more concise, highlighting the main findings and contributions of the article, and avoiding repetition of the previous content.
- Line 23, Replace "often causes organ dysfunction and even mortality" with "frequently results in organ dysfunction and mortality".
- Line 27, Change "eliminating invading pathogens and mitigating sepsis-induced dysregulated inflammation" to "eradicating invading pathogens and moderating sepsis-induced inflammation".
- Line 71, “Additionally” revised to“Furthermore”.
- Line 152-154, “This finding aligns with our previous reports that pro-DCD attenuated KC/GRO-α production in innate immune cells stimulated with exogenous bacterial endotoxins (e.g., LPS) or endogenous mediators of lethal endotoxemia and sepsis.” could revise to“This finding is consistent with our previous reports indicating that pro-DCD attenuates KC/GRO-α production in innate immune cells stimulated with exogenous bacterial endotoxins (e.g., LPS) or endogenous mediators of lethal endotoxemia and sepsis.”
Author Response
The manuscript, titled "Pro-dermcidin as an emerging regulator of innate immunity in sepsis", explores the immunomodulatory role of the precursor antimicrobial peptide pro-dermcidin (pro-DCD) in sepsis. The article has reasonable structure, clear logic and detailed data, which has high scientific value and potential clinical significance. However, there are also some areas for improvement, and here are the review comments on the article.
- To explore the specific mechanism of action of pro-DCD in sepsis, including how it regulates the immune response and promotes bacterial clearance. Propose new hypotheses and research directions. For example, innate immune signaling pathways TLR and STING (Reference: 1. José E Belizário. "Role of skin antimicrobial peptides in the pathogenesis of psoriasis, atopic dermatitis and hidradenitis suppurative: Highlights on dermcidin." Clinical Immunology Communications (2025); 2. PMID: 39939798 DOI: 10.1038/s41418-025-01457-z(2025)).
We appreciate the reviewer’s suggestion, and have outlined some future research directions (Line 212-223). Specifically, we propose future investigations to understand the role of dermcidin receptors (e.g., EGFR and ST2) and innate immune signaling pathways (e.g., TLR4 and SING) in regulating pro-DCD-mediated innate immunity and bacterial clearance in the revised manuscript.
- References: Some of the cited references is relatively old, and it is suggested to supplement the important research progress in related fields in recent years to enhance the timeliness and persuasiveness of the articles.
We appreciate the reviewer’s comments, and have provided several new references (#7, #8, #12, #36, #37, #38, #52, and #53) to the revised manuscript.
- Conclusion should be more concise, highlighting the main findings and contributions of the article, and avoiding repetition of the previous content.
We have significantly shortened the conclusions of the revised manuscript.
- Line 23, Replace "often causes organ dysfunction and even mortality" with "frequently results in organ dysfunction and mortality".
Revised as suggested.
- Line 27, Change "eliminating invading pathogens and mitigating sepsis-induced dysregulated inflammation" to "eradicating invading pathogens and moderating sepsis-induced inflammation".
Revised as suggested.
- Line 71, “Additionally” revised to“Furthermore”.
Revised as suggested.
- Line 152-154, “This finding aligns with our previous reports that pro-DCD attenuated KC/GRO-α production in innate immune cells stimulated with exogenous bacterial endotoxins (e.g., LPS) or endogenous mediators of lethal endotoxemia and sepsis.” could revise to“This finding is consistent with our previous reports indicating that pro-DCD attenuates KC/GRO-α production in innate immune cells stimulated with exogenous bacterial endotoxins (e.g., LPS) or endogenous mediators of lethal endotoxemia and sepsis.”
Revised as suggested (now Line 148).
Reviewer 2 Report
Comments and Suggestions for AuthorsThe review by Lou et al, “Pro-dermcidin as an emerging regulator of innate immunity in sepsis ” aims to describe the evidence of the pro-dermcidin (pro-DCD) role as a regulator of innate immunity in sepsis. Generally, I don’t think it can be considered as standard review, perhaps some mini-review category would be more appropriate( I am not sure that IJMS accepts the mini-reviews for publication). Authors tried to emphasize the findings by breaking the manuscript into several sections; however, I found it difficult to follow in some parts. Some parts of the text are too concisely written and the reader should search and read the publications to understand what authors wished to emphasize. It also seems to me that majority of data is a retrospective of the two most significant findings from the references 7 and 14, one of which is an abstract and yet is a part of the great deal of the manuscript (review). My opinion is that manuscript needs to be rewritten by adding literature details and explanations which would make the article more informative and easy to follow.
Author Response
The review by Lou et al, “Pro-dermcidin as an emerging regulator of innate immunity in sepsis ” aims to describe the evidence of the pro-dermcidin (pro-DCD) role as a regulator of innate immunity in sepsis. Generally, I don’t think it can be considered as standard review, perhaps some mini-review category would be more appropriate( I am not sure that IJMS accepts the mini-reviews for publication). Authors tried to emphasize the findings by breaking the manuscript into several sections; however, I found it difficult to follow in some parts. Some parts of the text are too concisely written and the reader should search and read the publications to understand what authors wished to emphasize. It also seems to me that majority of data is a retrospective of the two most significant findings from the references 7 and 14, one of which is an abstract and yet is a part of the great deal of the manuscript (review). My opinion is that manuscript needs to be rewritten by adding literature details and explanations which would make the article more informative and easy to follow.
The manuscript has been revised to include additional references (#7, #8, #12, #36, #37, #38, #52, and #53), clarify several section headings, remove some information pertaining to reference 18, and incorporate a paragraph discussing future research directions (Lines 212-223).
Reviewer 3 Report
Comments and Suggestions for AuthorsThe discussed issue of the importance of pro-dermicin as a regulator of non-specific response in the course of sepsis is interesting, with potential practical application. However, the presented study does not meet the expectations related to the topic and is based mainly on citations of own works published in 2024 and 2025. Therefore, it is difficult to treat the presented material as a new perspective on the role of pro-dermicin in the regulation of innate immunity.
Comments on the Quality of English LanguageThe discussed issue of the importance of pro-dermicin as a regulator of non-specific response in the course of sepsis is interesting, with potential practical application. However, the presented study does not meet the expectations related to the topic and is based mainly on citations of own works published in 2024 and 2025. Therefore, it is difficult to treat the presented material as a new perspective on the role of pro-dermicin in the regulation of innate immunity.
Author Response
The discussed issue of the importance of pro-dermicin as a regulator of non-specific response in the course of sepsis is interesting, with potential practical application. However, the presented study does not meet the expectations related to the topic and is based mainly on citations of own works published in 2024 and 2025. Therefore, it is difficult to treat the presented material as a new perspective on the role of pro-dermicin in the regulation of innate immunity.
The manuscript has been revised to include additional references (#7, #8, #12, #36, #37, #38, #52, and #53), clarify several section headings, remove some information pertaining to reference 18, and incorporate a paragraph discussing future research directions (Lines 212-223).
Reviewer 4 Report
Comments and Suggestions for AuthorsThe review article titled ‘Pro-dermcidin as an emerging regulator of innate immunity in sepsis’ Lou et al. comprehensively summarized the recent evidence supporting pro-dermcidin (DCD) as a regulator of innate immunity in sepsis and proposed as a therapeutic molecule for inflammatory diseases like sepsis. The pro-DCD, believed to be an inducible protein secreted by eccrine sweat glands and innate immune cells that is processed into the mature form DCD. The anti-pro-DCD antibodies showed improvement in overall immune response suggesting the protective role of pr-DCD during sepsis. The Pro-DCD also elicits autophagy measured by the conversation of LC-II and GFP-LC3 puncta formation. PEGylated- pro-DCD-C34S reduced sepsis-induced inflammation and bacterial dissemination. Based on these observations the authors claim that pro-DCD derivatives have therapeutic potential against lethal microbial infections.
The manuscript is well written, but it requires more molecular specifics, and the interactive figures necessitate detailed information. The citation pattern also requires refinement (ref 7 is pretty much similar to ref 14). The manuscript can provide unique insights, given that the authors are among the leading groups in the field, into how to shape the future trajectory of pro-dermcidin and sepsis research.
Author Response
The review article titled ‘Pro-dermcidin as an emerging regulator of innate immunity in sepsis’ Lou et al. comprehensively summarized the recent evidence supporting pro-dermcidin (DCD) as a regulator of innate immunity in sepsis and proposed as a therapeutic molecule for inflammatory diseases like sepsis. The pro-DCD, believed to be an inducible protein secreted by eccrine sweat glands and innate immune cells that is processed into the mature form DCD. The anti-pro-DCD antibodies showed improvement in overall immune response suggesting the protective role of pr-DCD during sepsis. The Pro-DCD also elicits autophagy measured by the conversation of LC-II and GFP-LC3 puncta formation. PEGylated- pro-DCD-C34S reduced sepsis-induced inflammation and bacterial dissemination. Based on these observations the authors claim that pro-DCD derivatives have therapeutic potential against lethal microbial infections.
The manuscript is well written, but it requires more molecular specifics, and the interactive figures necessitate detailed information. The citation pattern also requires refinement (ref 7 is pretty much similar to ref 14). The manuscript can provide unique insights, given that the authors are among the leading groups in the field, into how to shape the future trajectory of pro-dermcidin and sepsis research.
The manuscript has been revised to include additional references (#7, #8, #12, #36, #37, #38, #52, and #53), clarify several section headings, remove some information pertaining to reference 18, and incorporate a paragraph discussing future research directions (Lines 212-223).
Round 2
Reviewer 2 Report
Comments and Suggestions for AuthorsThe manuscript is improved.
Reviewer 3 Report
Comments and Suggestions for AuthorsThe authors' response is unclear. In my opinion, nothing in the manuscript has changed. I don't see any additional footnotes or explanations for the section headings. The information about including a paragraph discussing future research directions (212-223) is incorrect; the text on this topic has not changed.
Reviewer 4 Report
Comments and Suggestions for AuthorsThe authors have addressed the concerns and revised manuscript is suitable for the publication.
