Effects of T cell leptin signaling on systemic glucose tolerance and T cell responses in obesity

Kaitlin Kiernan; Amanda G. Nichols; Yazan Alwarawrah; Nancie J. MacIver

doi:10.1371/journal.pone.0286470

Peer Review History

Original SubmissionFebruary 2, 2023
17 Mar 2023 Decision Letter - Sadiq Umar, Editor PONE-D-23-03100 Effects of T cell leptin signaling on systemic glucose tolerance and T cell responses in obesity PLOS ONE Dear Dr. MacIver, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Apr 30 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: No Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: - Authors need to revise the structure of results section. Please structure with proper subsections and describe your results separately; not only with Figures legends/captions. Also, figure legends should be submitted in a different section or along with figures. - Why you didn't check lipid profile? What about systemic effects of hypercholesterolimia? It greatly trigger cardiovascular and immune response. Please justify. - You could also take pictures of spleen from each mice. Could help justify splenomegaly! - Study could elaborate several other factors and parameters of systemic inflammation. Why didn't you do that. Please justify other possible limitations. Reviewer #2: In this article, the authors have focused on understanding the leptin signaling pathway driving T-cell inflammation in obesity. This is a well-written manuscript with minor correction that needs to be addressed, Line 61 Expand Rag-/- Quote reference for all the protocols followed in the method section Line 148 quote the company Include Scatter plot for flow cytometry Give a line of reason for every result stated in the study. For example, why are the metabolism and function affected in CD4+ T cells when compared to CD8+ T cells? Check for grammatical mistakes throughout the manuscript ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. 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Revision 1
15 May 2023 Author Response Response to reviewers We thank the reviewers for their careful review of our manuscript. We have addressed all reviewer comments below and now present an improved manuscript for review. Reviewer #1: 1. Authors need to revise the structure of results section. Please structure with proper subsections and describe your results separately; not only with Figures legends/captions. Also, figure legends should be submitted in a different section or along with figures. Thank you for this suggestion. We agree that adding subsections would improve the structure of the manuscript. In response to this comment, subsections were added to the results section. Figure legends are placed in the text as per PLOS manuscript guidelines. 2. Why you didn't check lipid profile? What about systemic effects of hypercholesterolemia? It greatly trigger cardiovascular and immune response. Please justify. Thank you for this comment. We agree that systemic effects of hypercholesterolemia could be impacted in our mouse model and subsequently influence T cell responses. In response to this comment, we performed lipid analyses on serum samples from this study. Please see Supplemental Figure 2. We did not see any significant differences in total cholesterol or triglyceride levels between the experimental groups. 3. You could also take pictures of spleen from each mice. Could help justify splenomegaly! While we did not have photographs of the spleens from these mice, we did record spleen weights and weight of visceral adipose tissue, so we have included that information in the response to reviewers attached file and in the revised cover page. 4. Study could elaborate several other factors and parameters of systemic inflammation. Why didn't you do that. Please justify other possible limitations. Thank you for this comment. We agree that more markers and parameters of systemic inflammation would be informative. In response to this comment, we performed multiplex analysis on serum samples from our mouse cohort. We assessed serum levels of TNF, IFN-γ, IL-17, IL-1β, and IL-6. We did not find any significant differences in serum cytokine levels between the groups. We also performed a leptin ELISA to measure serum leptin levels in these mice. This data is included in Supplemental Figures 1 and 3. Reviewer #2: 1. In this article, the authors have focused on understanding the leptin signaling pathway driving T-cell inflammation in obesity. This is a well-written manuscript with minor correction that needs to be addressed, Line 61 Expand Rag-/- Quote reference for all the protocols followed in the method section Line 148 quote the company Include Scatter plot for flow cytometry Give a line of reason for every result stated in the study. For example, why are the metabolism and function affected in CD4+ T cells when compared to CD8+ T cells? Check for grammatical mistakes throughout the manuscript We thank the reviewer for these helpful comments. In response to the comments from this reviewer, changes to the text were made, including expanding on “Rag-/-” to clarify, referencing our publications where methods have been published previously, and including several sentences explaining the results presented. We also included flow cytometry scatter plots in Supplemental Figure 2. Attachments Attachment Submitted filename: Response to reviewers.docx https://doi.org/10.1371/journal.pone.0286470.r002
17 May 2023 Decision Letter - Sadiq Umar, Editor Effects of T cell leptin signaling on systemic glucose tolerance and T cell responses in obesity PONE-D-23-03100R1 Dear Dr. MacIver, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Sadiq Umar Academic Editor PLOS ONE Additional Editor Comments (optional): Recommendation for acceptance. Reviewers' comments: https://doi.org/10.1371/journal.pone.0286470.r003
Formally Accepted
24 May 2023 Acceptance Letter - Sadiq Umar, Editor PONE-D-23-03100R1 Effects of T cell leptin signaling on systemic glucose tolerance and T cell responses in obesity Dear Dr. MacIver: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Sadiq Umar Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0286470.r004

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