Reviewer’s report
Title: 
Increased V
δ
1 
γδ
T cells Predominantly Contributed to IL-17 Production
in the Development of Adult Human Post-infectious Irritable Bowel Syndrome
Version: 
3 
Date: 
22 Jan 2021
Reviewer's report:
In the manuscript Increased V
δ
1 
γδ
T cells Predominantly Contributed 1 to IL-17
Production
in the Development of Adult Human Post-infectious Irritable Bowel Syndrome
by LW Dong et al. the authors aimed 
to investigate further on the functionally
predominant subset of gd T cells producing IL-17 and its role in post-infectious
irritable bowel diseas (PI-IBS).
The main results are that V
δ
1 gd T cells significantly increased while V
δ
2 gd T
cells remained unchanged in both the peripheral blood and local colonic tissue
from PI-IBS patients (P<0.05). 2. When cultured in vitro, the V
δ
1 gd T cells
remarkably proliferated, activated and produced IL-17. The authors conclude
that V
δ
1 gd T cells was the predominant gd T cells subset in both peripheral and
intestinal tissue, and was the major IL-17 producing
gd T cells in PI-IBS.
The focus on the betadelta T cell located in the barrier site in GI tract most likely
a pivotal role in the immunotolerance as these cells can easily be activated by
homing to the intestinal epithelium and interact with microbiota- a relative new
knowledge with still many unresolved questions including the role of IL17, IFN
among other cytokines. 
This is also a follow-up study from the research group
showed that the heath shock protein 70 the 
γδ
 T cells' phenotype and function
during PI-IBS in a mouse model. Therefore, the aim of this study is highly
justified..
In general, the study is well designed appropriate methods used, original data are
presented and valid conclusions are made.
I have the following area of concerns
1. In the introduction there is a lack of a condensed review of PI-IBS with focus
on pathophysiological mechanisms with reference to new review articles-as a
low grade chronic inflammatory condition. Moreover, also some background on
IL-17 and the relevance in IBS- there are also some references in PI-IBS
2. The PI-IBS group should be better characterized. Microbiology tests. Was the
histological examination of colon biopsies- normal without any inflammatory
cells? What GI diagnosis were excluded with ordinary examinations (celiac
disease etc). What type of IBS (diarrhoea, constipation? both?). 
3. The healthy volunteers should be better characterized. Sex, age, GI
symptoms? Any immunological diseases such as rheumatoid arthritis. Was a
colonoscopy with histological examinations done to exclude any disease? 
4. Statistics. Students' t-tests were used- were data normal distributed?
5. What commercial ELISA was used? Data on detection limits etc of. IFN
γ
 and
IL-17. Were all samples > detection limit? This is often a problem using ELISA
methods in measurement of cytokines. 
6. In the Discussion, there is a lack of strength and weakness of the study 
Conclusion
The manuscript has a good scientific value with appropriate methods used, but
improvements have to be done before valid conclusions can be made.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
Yes
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Reviewer’s report
Title: 
Increased V
δ
1 
γδ
T cells Predominantly Contributed to IL-17 Production
in the Development of Adult Human Post-infectious Irritable Bowel Syndrome
Version: 
3 
Date: 
22 Jan 2021
Reviewer's report:
In the manuscript Increased V
δ
1 
γδ
T cells Predominantly Contributed 1 to IL-17
Production
in the Development of Adult Human Post-infectious Irritable Bowel Syndrome
by LW Dong et al. the authors aimed 
to investigate further on the functionally
predominant subset of gd T cells producing IL-17 and its role in post-infectious
irritable bowel diseas (PI-IBS).
The main results are that V
δ
1 gd T cells significantly increased while V
δ
2 gd T
cells remained unchanged in both the peripheral blood and local colonic tissue
from PI-IBS patients (P<0.05). 2. When cultured in vitro, the V
δ
1 gd T cells
remarkably proliferated, activated and produced IL-17. The authors conclude
that V
δ
1 gd T cells was the predominant gd T cells subset in both peripheral and
intestinal tissue, and was the major IL-17 producing
gd T cells in PI-IBS.
The focus on the betadelta T cell located in the barrier site in GI tract most likely
a pivotal role in the immunotolerance as these cells can easily be activated by
homing to the intestinal epithelium and interact with microbiota- a relative new
knowledge with still many unresolved questions including the role of IL17, IFN
among other cytokines. 
This is also a follow-up study from the research group
showed that the heath shock protein 70 the 
γδ
 T cells' phenotype and function
during PI-IBS in a mouse model. Therefore, the aim of this study is highly
justified..
In general, the study is well designed appropriate methods used, original data are
presented and valid conclusions are made.
I have the following area of concerns
1. In the introduction there is a lack of a condensed review of PI-IBS with focus
on pathophysiological mechanisms with reference to new review articles-as a
low grade chronic inflammatory condition. Moreover, also some background on
IL-17 and the relevance in IBS- there are also some references in PI-IBS
2. The PI-IBS group should be better characterized. Microbiology tests. Was the
histological examination of colon biopsies- normal without any inflammatory
cells? What GI diagnosis were excluded with ordinary examinations (celiac
disease etc). What type of IBS (diarrhoea, constipation? both?). 
3. The healthy volunteers should be better characterized. Sex, age, GI
symptoms? Any immunological diseases such as rheumatoid arthritis. Was a
colonoscopy with histological examinations done to exclude any disease? 
4. Statistics. Students' t-tests were used- were data normal distributed?
5. What commercial ELISA was used? Data on detection limits etc of. IFN
γ
 and
IL-17. Were all samples > detection limit? This is often a problem using ELISA
methods in measurement of cytokines. 
6. In the Discussion, there is a lack of strength and weakness of the study 
Conclusion
The manuscript has a good scientific value with appropriate methods used, but
improvements have to be done before valid conclusions can be made.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
Yes
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Please review this paper.
user
Reviewer’s report
Title: 
Increased V
δ
1 
γδ
T cells Predominantly Contributed to IL-17 Production
in the Development of Adult Human Post-infectious Irritable Bowel Syndrome
Version: 
3 
Date: 
22 Jan 2021
Reviewer's report:
In the manuscript Increased V
δ
1 
γδ
T cells Predominantly Contributed 1 to IL-17
Production
in the Development of Adult Human Post-infectious Irritable Bowel Syndrome
by LW Dong et al. the authors aimed 
to investigate further on the functionally
predominant subset of gd T cells producing IL-17 and its role in post-infectious
irritable bowel diseas (PI-IBS).
The main results are that V
δ
1 gd T cells significantly increased while V
δ
2 gd T
cells remained unchanged in both the peripheral blood and local colonic tissue
from PI-IBS patients (P<0.05). 2. When cultured in vitro, the V
δ
1 gd T cells
remarkably proliferated, activated and produced IL-17. The authors conclude
that V
δ
1 gd T cells was the predominant gd T cells subset in both peripheral and
intestinal tissue, and was the major IL-17 producing
gd T cells in PI-IBS.
The focus on the betadelta T cell located in the barrier site in GI tract most likely
a pivotal role in the immunotolerance as these cells can easily be activated by
homing to the intestinal epithelium and interact with microbiota- a relative new
knowledge with still many unresolved questions including the role of IL17, IFN
among other cytokines. 
This is also a follow-up study from the research group
showed that the heath shock protein 70 the 
γδ
 T cells' phenotype and function
during PI-IBS in a mouse model. Therefore, the aim of this study is highly
justified..
In general, the study is well designed appropriate methods used, original data are
presented and valid conclusions are made.
I have the following area of concerns
1. In the introduction there is a lack of a condensed review of PI-IBS with focus
on pathophysiological mechanisms with reference to new review articles-as a
low grade chronic inflammatory condition. Moreover, also some background on
IL-17 and the relevance in IBS- there are also some references in PI-IBS
2. The PI-IBS group should be better characterized. Microbiology tests. Was the
histological examination of colon biopsies- normal without any inflammatory
cells? What GI diagnosis were excluded with ordinary examinations (celiac
disease etc). What type of IBS (diarrhoea, constipation? both?). 
3. The healthy volunteers should be better characterized. Sex, age, GI
symptoms? Any immunological diseases such as rheumatoid arthritis. Was a
colonoscopy with histological examinations done to exclude any disease? 
4. Statistics. Students' t-tests were used- were data normal distributed?
5. What commercial ELISA was used? Data on detection limits etc of. IFN
γ
 and
IL-17. Were all samples > detection limit? This is often a problem using ELISA
methods in measurement of cytokines. 
6. In the Discussion, there is a lack of strength and weakness of the study 
Conclusion
The manuscript has a good scientific value with appropriate methods used, but
improvements have to be done before valid conclusions can be made.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
Yes
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
assistant