Title: Hepatic recruitment of myeloid-derived suppressor cells upon liver injury promotes both
liver regeneration and fibrosis
Version: 4 Date: 08 Aug 2023
Reviewer's report:
I cannot agree with the authors’ points for my question number 1.
https://pubmed.ncbi.nlm.nih.gov/21980263/
The reference paper that the authors referred to is showing HGF expression in PMN-MDSC. In
this manuscript, the authors clearly showed that M-MDSC are main MDSC recruited by liver
inflammation in Fig.3. Also, in the gated population in Fig.3A, the mean fluorescence intensity
of HGF in 24 h is not higher than 0h control. Based on this result, it is difficult to conclude
that HGF is expressed by hepatitis-related MDSCs. Further experiments are necessary to prove
that HGF is expressed by hepatitis-related MDSCs as well as MDSCs in the authors' co-culture
model.
https://pubmed.ncbi.nlm.nih.gov/31552179/
Thank you very much  for providing this information showing the up-regulation of VEGF in
MDSCs.
https://pubmed.ncbi.nlm.nih.gov/16828470/
I think that the authors misinterpreted this paper. In this reference paper, after 48 h treatment of
TGF-beta, the survival cells were analyzed and those survivors showed resistance to apoptosis.
In the authors’ manuscript, they are testing the effect of TGF-beta during the co-culture which
is more similar to the paper by Oberhammer et al. in PNAS.
https://pubmed.ncbi.nlm.nih.gov/26839553/
In this reference paper, the authors treated TGF-beta to hepatic progenitor cells (12 or 48 h),
then performed co-culture with HSCs. The experimental method is not the same as the authors
did in this manuscript.
Overall, it is hard to accept the authors’ rebuttals including the following.
We interpret these findings as possible evidence of context-dependent effects of TGF-,
depending on factors such as concentration and duration of exposure. In our co-culture study, we
propose that MDSCs promote the activation of HSCs via a cocktail of different cytokines, which
include TGF- and IL-10. Further study is needed to fully elucidate these intricate interactions
and their implications for liver repair.”.
Revision experiment is needed to accept this manuscript. The author mentioned that the cocktail
of different cytokines including TGF-beta and IL-10 promoted activation of HSCs. I was
wondering whether the treatment of TGF-beta plus IL-10 to hepatocytes or HSCs will promote
their proliferation. Or the cocktail of TGF-beta, IL-10, VEGF and HGF will activate HSCs?
The current version of the manuscript requires further supporting data to be published.
Title: Hepatic recruitment of myeloid-derived suppressor cells upon liver injury promotes both
liver regeneration and fibrosis
Version: 4 Date: 08 Aug 2023
Reviewer's report:
I cannot agree with the authors’ points for my question number 1.
https://pubmed.ncbi.nlm.nih.gov/21980263/
The reference paper that the authors referred to is showing HGF expression in PMN-MDSC. In
this manuscript, the authors clearly showed that M-MDSC are main MDSC recruited by liver
inflammation in Fig.3. Also, in the gated population in Fig.3A, the mean fluorescence intensity
of HGF in 24 h is not higher than 0h control. Based on this result, it is difficult to conclude
that HGF is expressed by hepatitis-related MDSCs. Further experiments are necessary to prove
that HGF is expressed by hepatitis-related MDSCs as well as MDSCs in the authors' co-culture
model.
https://pubmed.ncbi.nlm.nih.gov/31552179/
Thank you very much  for providing this information showing the up-regulation of VEGF in
MDSCs.
https://pubmed.ncbi.nlm.nih.gov/16828470/
I think that the authors misinterpreted this paper. In this reference paper, after 48 h treatment of
TGF-beta, the survival cells were analyzed and those survivors showed resistance to apoptosis.
In the authors’ manuscript, they are testing the effect of TGF-beta during the co-culture which
is more similar to the paper by Oberhammer et al. in PNAS.
https://pubmed.ncbi.nlm.nih.gov/26839553/
In this reference paper, the authors treated TGF-beta to hepatic progenitor cells (12 or 48 h),
then performed co-culture with HSCs. The experimental method is not the same as the authors
did in this manuscript.
Overall, it is hard to accept the authors’ rebuttals including the following.
We interpret these findings as possible evidence of context-dependent effects of TGF-,
depending on factors such as concentration and duration of exposure. In our co-culture study, we
propose that MDSCs promote the activation of HSCs via a cocktail of different cytokines, which
include TGF- and IL-10. Further study is needed to fully elucidate these intricate interactions
and their implications for liver repair.”.
Revision experiment is needed to accept this manuscript. The author mentioned that the cocktail
of different cytokines including TGF-beta and IL-10 promoted activation of HSCs. I was
wondering whether the treatment of TGF-beta plus IL-10 to hepatocytes or HSCs will promote
their proliferation. Or the cocktail of TGF-beta, IL-10, VEGF and HGF will activate HSCs?
The current version of the manuscript requires further supporting data to be published.
Please review this paper.
user
Title: Hepatic recruitment of myeloid-derived suppressor cells upon liver injury promotes both
liver regeneration and fibrosis
Version: 4 Date: 08 Aug 2023
Reviewer's report:
I cannot agree with the authors’ points for my question number 1.
https://pubmed.ncbi.nlm.nih.gov/21980263/
The reference paper that the authors referred to is showing HGF expression in PMN-MDSC. In
this manuscript, the authors clearly showed that M-MDSC are main MDSC recruited by liver
inflammation in Fig.3. Also, in the gated population in Fig.3A, the mean fluorescence intensity
of HGF in 24 h is not higher than 0h control. Based on this result, it is difficult to conclude
that HGF is expressed by hepatitis-related MDSCs. Further experiments are necessary to prove
that HGF is expressed by hepatitis-related MDSCs as well as MDSCs in the authors' co-culture
model.
https://pubmed.ncbi.nlm.nih.gov/31552179/
Thank you very much  for providing this information showing the up-regulation of VEGF in
MDSCs.
https://pubmed.ncbi.nlm.nih.gov/16828470/
I think that the authors misinterpreted this paper. In this reference paper, after 48 h treatment of
TGF-beta, the survival cells were analyzed and those survivors showed resistance to apoptosis.
In the authors’ manuscript, they are testing the effect of TGF-beta during the co-culture which
is more similar to the paper by Oberhammer et al. in PNAS.
https://pubmed.ncbi.nlm.nih.gov/26839553/
In this reference paper, the authors treated TGF-beta to hepatic progenitor cells (12 or 48 h),
then performed co-culture with HSCs. The experimental method is not the same as the authors
did in this manuscript.
Overall, it is hard to accept the authors’ rebuttals including the following.
We interpret these findings as possible evidence of context-dependent effects of TGF-,
depending on factors such as concentration and duration of exposure. In our co-culture study, we
propose that MDSCs promote the activation of HSCs via a cocktail of different cytokines, which
include TGF- and IL-10. Further study is needed to fully elucidate these intricate interactions
and their implications for liver repair.”.
Revision experiment is needed to accept this manuscript. The author mentioned that the cocktail
of different cytokines including TGF-beta and IL-10 promoted activation of HSCs. I was
wondering whether the treatment of TGF-beta plus IL-10 to hepatocytes or HSCs will promote
their proliferation. Or the cocktail of TGF-beta, IL-10, VEGF and HGF will activate HSCs?
The current version of the manuscript requires further supporting data to be published.
assistant