Reviewer's report
Title:Deletion of Foxp3+ regulatory T cells in genetically targeted mice supports
development of intestinal inflammation
Version: 1Date:22 September 2010
Reviewer: Holm Uhlig
Reviewer's report:
Boehm et al. investigate the role of Foxp3+ regulatory T cells in intestinal
inflammation. In humans with IPEX syndrome and Foxp3 mutations intestinal
inflammation is found in many patients. Although there is strong evidence for the
role of these cells in several mouse model situations of intestinal inflammation
the understanding is still not absolutely clear since Foxp3 knockout mice develop
inflammation in several organs but typically not in the colon.
The authors aim to investigate the role of Foxp3+ cells by using a transgenic
system to deplete Foxp3+ cells that express DTR using DT. The finding that
deletion of Treg in mice with a functional immune system induces inflammation in
lung or liver, but hardly in the colon is consistent with previous findings in Foxp3+
knockout mice. However, the authors show a role for Foxp3+ cells in chemical
induced acute colitis as well as in the T cell transfer system. In these specific
model situations lack of Foxp3+ cells act as aggravating factor. Again, this is not
particular new since it has been shown by other authors using different depletion
methods.
The number of mice used for the different experiments are small and data about
repeat experiments are not clearly documented.
Minor points:
Method section Immunohistochemistry Sections were …pretreated with 3%
hydrogen peroxide … (and not hydrogenperoxidase as stated in the manuscript) I
wonder if the student t-test is appropriate for the evaluation of statistical
differences since for these kind of experiments it is typically not possible to show
a normal distribution of the measures. The Mann-Whitney U test is likely to be
more appropriate.
“Deletion of Treg is the onset of chronic T cell-mediated intestinal inflammation”
??
Reviewer's report
Title:Deletion of Foxp3+ regulatory T cells in genetically targeted mice supports
development of intestinal inflammation
Version: 1Date:22 September 2010
Reviewer: Holm Uhlig
Reviewer's report:
Boehm et al. investigate the role of Foxp3+ regulatory T cells in intestinal
inflammation. In humans with IPEX syndrome and Foxp3 mutations intestinal
inflammation is found in many patients. Although there is strong evidence for the
role of these cells in several mouse model situations of intestinal inflammation
the understanding is still not absolutely clear since Foxp3 knockout mice develop
inflammation in several organs but typically not in the colon.
The authors aim to investigate the role of Foxp3+ cells by using a transgenic
system to deplete Foxp3+ cells that express DTR using DT. The finding that
deletion of Treg in mice with a functional immune system induces inflammation in
lung or liver, but hardly in the colon is consistent with previous findings in Foxp3+
knockout mice. However, the authors show a role for Foxp3+ cells in chemical
induced acute colitis as well as in the T cell transfer system. In these specific
model situations lack of Foxp3+ cells act as aggravating factor. Again, this is not
particular new since it has been shown by other authors using different depletion
methods.
The number of mice used for the different experiments are small and data about
repeat experiments are not clearly documented.
Minor points:
Method section Immunohistochemistry Sections were …pretreated with 3%
hydrogen peroxide … (and not hydrogenperoxidase as stated in the manuscript) I
wonder if the student t-test is appropriate for the evaluation of statistical
differences since for these kind of experiments it is typically not possible to show
a normal distribution of the measures. The Mann-Whitney U test is likely to be
more appropriate.
“Deletion of Treg is the onset of chronic T cell-mediated intestinal inflammation”
??
Please review this paper.
user
Reviewer's report
Title:Deletion of Foxp3+ regulatory T cells in genetically targeted mice supports
development of intestinal inflammation
Version: 1Date:22 September 2010
Reviewer: Holm Uhlig
Reviewer's report:
Boehm et al. investigate the role of Foxp3+ regulatory T cells in intestinal
inflammation. In humans with IPEX syndrome and Foxp3 mutations intestinal
inflammation is found in many patients. Although there is strong evidence for the
role of these cells in several mouse model situations of intestinal inflammation
the understanding is still not absolutely clear since Foxp3 knockout mice develop
inflammation in several organs but typically not in the colon.
The authors aim to investigate the role of Foxp3+ cells by using a transgenic
system to deplete Foxp3+ cells that express DTR using DT. The finding that
deletion of Treg in mice with a functional immune system induces inflammation in
lung or liver, but hardly in the colon is consistent with previous findings in Foxp3+
knockout mice. However, the authors show a role for Foxp3+ cells in chemical
induced acute colitis as well as in the T cell transfer system. In these specific
model situations lack of Foxp3+ cells act as aggravating factor. Again, this is not
particular new since it has been shown by other authors using different depletion
methods.
The number of mice used for the different experiments are small and data about
repeat experiments are not clearly documented.
Minor points:
Method section Immunohistochemistry Sections were …pretreated with 3%
hydrogen peroxide … (and not hydrogenperoxidase as stated in the manuscript) I
wonder if the student t-test is appropriate for the evaluation of statistical
differences since for these kind of experiments it is typically not possible to show
a normal distribution of the measures. The Mann-Whitney U test is likely to be
more appropriate.
“Deletion of Treg is the onset of chronic T cell-mediated intestinal inflammation”
??
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