Reviewer's report
Title:Immunoregulatory Actions of T cell PPARgamma at the Colonic Mucosa in
Mice with Experimental IBD
Version: 1Date:6 April 2010
Reviewer: Anje A te Velde
Reviewer's report:
This is an extensive study that investigates the role of PPAR # in T cells. A large
number of data of expression profiles after 7 days of DSS colitis result in different
conclusions. Some of the findings and interpretations raise questions:
The interpretation of the data in figure 1A and B is somewhat optimistic:
“Differences between the groups first appeared on day 4 of the
challenge, where CD4cre mice had a significantly worsened disease activity
index (DAI) and significantly greater body weight loss (Figure 1A and 1B)”.
I see a significant difference on day 4 of the DAI and on day 4 and 5 of the
bodyweight, that’s all.
“As anticipated from a model that initially targets epithelial cells and
macrophages, no histological differences were found
between WT and CD4cre mice on day 2”. Why is there a difference in foxp3 cells
on day 2 in the spleen?
Why is foxp3 used in blood and spleen and in MLN IL-10?
IL-10 is already low at t=0, increases at t=2 and decreases again at day 7 in the
MLN, what does this mean?
In the discussion it is mentioned that T cells are recruited at
later stages of disease (days 4-7) following the initial epithelial cell damage and
macrophage activation. Did you observe this? In figure 2 leukocyte infiltration is
scored, it will be of interest to demonstrate if this is a mononuclear or a
polymorphonuclear infiltrate or both.
In a paper of Melgar et al, Am J Physiol Gastrointest Liver Physiol, 2005 they
indicate that involvement of the T cell reaction in the DSS model is in the later
stage of disease after day 7. The model as it is used is an acute model of colonic
inflammation.
In figure 6 there is almost no upregulation of the pro-inflammatory genes in the
WT mice. How does this match literature?
It would be interesting to discuss the differences found in DSS experiments with
deficiency of PPAR # in epithelial cells and macrophages as mentioned in the
introduction (actual findings). In the discussion there is no extra information on
this available. This would give more information on the cell specific nature of the
role of PPAR #.
The title of the paper: “Immunoregulatory Actions of T cell PPAR # at the Colonic
Mucosa in Mice with Experimental IBD” indicates that certain actions of the T
cells are studied. The gene expression induction is secondary to supposed
actions that are not directly studied.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests
Reviewer's report
Title:Immunoregulatory Actions of T cell PPARgamma at the Colonic Mucosa in
Mice with Experimental IBD
Version: 1Date:6 April 2010
Reviewer: Anje A te Velde
Reviewer's report:
This is an extensive study that investigates the role of PPAR # in T cells. A large
number of data of expression profiles after 7 days of DSS colitis result in different
conclusions. Some of the findings and interpretations raise questions:
The interpretation of the data in figure 1A and B is somewhat optimistic:
“Differences between the groups first appeared on day 4 of the
challenge, where CD4cre mice had a significantly worsened disease activity
index (DAI) and significantly greater body weight loss (Figure 1A and 1B)”.
I see a significant difference on day 4 of the DAI and on day 4 and 5 of the
bodyweight, that’s all.
“As anticipated from a model that initially targets epithelial cells and
macrophages, no histological differences were found
between WT and CD4cre mice on day 2”. Why is there a difference in foxp3 cells
on day 2 in the spleen?
Why is foxp3 used in blood and spleen and in MLN IL-10?
IL-10 is already low at t=0, increases at t=2 and decreases again at day 7 in the
MLN, what does this mean?
In the discussion it is mentioned that T cells are recruited at
later stages of disease (days 4-7) following the initial epithelial cell damage and
macrophage activation. Did you observe this? In figure 2 leukocyte infiltration is
scored, it will be of interest to demonstrate if this is a mononuclear or a
polymorphonuclear infiltrate or both.
In a paper of Melgar et al, Am J Physiol Gastrointest Liver Physiol, 2005 they
indicate that involvement of the T cell reaction in the DSS model is in the later
stage of disease after day 7. The model as it is used is an acute model of colonic
inflammation.
In figure 6 there is almost no upregulation of the pro-inflammatory genes in the
WT mice. How does this match literature?
It would be interesting to discuss the differences found in DSS experiments with
deficiency of PPAR # in epithelial cells and macrophages as mentioned in the
introduction (actual findings). In the discussion there is no extra information on
this available. This would give more information on the cell specific nature of the
role of PPAR #.
The title of the paper: “Immunoregulatory Actions of T cell PPAR # at the Colonic
Mucosa in Mice with Experimental IBD” indicates that certain actions of the T
cells are studied. The gene expression induction is secondary to supposed
actions that are not directly studied.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests
Please review this paper.
user
Reviewer's report
Title:Immunoregulatory Actions of T cell PPARgamma at the Colonic Mucosa in
Mice with Experimental IBD
Version: 1Date:6 April 2010
Reviewer: Anje A te Velde
Reviewer's report:
This is an extensive study that investigates the role of PPAR # in T cells. A large
number of data of expression profiles after 7 days of DSS colitis result in different
conclusions. Some of the findings and interpretations raise questions:
The interpretation of the data in figure 1A and B is somewhat optimistic:
“Differences between the groups first appeared on day 4 of the
challenge, where CD4cre mice had a significantly worsened disease activity
index (DAI) and significantly greater body weight loss (Figure 1A and 1B)”.
I see a significant difference on day 4 of the DAI and on day 4 and 5 of the
bodyweight, that’s all.
“As anticipated from a model that initially targets epithelial cells and
macrophages, no histological differences were found
between WT and CD4cre mice on day 2”. Why is there a difference in foxp3 cells
on day 2 in the spleen?
Why is foxp3 used in blood and spleen and in MLN IL-10?
IL-10 is already low at t=0, increases at t=2 and decreases again at day 7 in the
MLN, what does this mean?
In the discussion it is mentioned that T cells are recruited at
later stages of disease (days 4-7) following the initial epithelial cell damage and
macrophage activation. Did you observe this? In figure 2 leukocyte infiltration is
scored, it will be of interest to demonstrate if this is a mononuclear or a
polymorphonuclear infiltrate or both.
In a paper of Melgar et al, Am J Physiol Gastrointest Liver Physiol, 2005 they
indicate that involvement of the T cell reaction in the DSS model is in the later
stage of disease after day 7. The model as it is used is an acute model of colonic
inflammation.
In figure 6 there is almost no upregulation of the pro-inflammatory genes in the
WT mice. How does this match literature?
It would be interesting to discuss the differences found in DSS experiments with
deficiency of PPAR # in epithelial cells and macrophages as mentioned in the
introduction (actual findings). In the discussion there is no extra information on
this available. This would give more information on the cell specific nature of the
role of PPAR #.
The title of the paper: “Immunoregulatory Actions of T cell PPAR # at the Colonic
Mucosa in Mice with Experimental IBD” indicates that certain actions of the T
cells are studied. The gene expression induction is secondary to supposed
actions that are not directly studied.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests
assistant