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Cutting Edge: Dab2 Is a FOXP3 Target Gene Required for Regulatory T Cell Function
Abstract
FOXP3-expressing regulatory T (Treg) cells are vital for maintaining peripheral T cell tolerance and homeostasis. The mechanisms by which FOXP3 target genes orchestrate context-dependent Treg cell function are largely unknown. In this study we show that in mouse peripheral lymphocytes the Drosophila Disabled-2 (Dab2) homolog, a gene that is involved in enhancing TGFβ responses, is exclusively expressed in FOXP3+ regulatory T cells. Dab2 is a direct target of FOXP3, and regulatory T cells lacking DAB2 are functionally impaired in vitro and in vivo. However, not all aspects of Treg cell function are perturbed, and DAB2 appears to be dispensable for Treg cell function in maintaining naive T cell homeostasis.
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Dab2 null Treg cells have no obvious phenotype in vivo.
“Immune system/Treg | No obvious phenotype in vivo; failed to suppress T cells”
From Endocytosis and Physiology: Insights from Disabled-2 Deficient Mice (2016) · cites this paper as Jain et al., 2009
In Results and Discussion, Dab2 conditional-knockout mice appeared healthy, lacked overt autoimmunity, and had phenotypically similar Treg cells under unperturbed conditions. But the same section reports an in vivo defect: their Treg cells failed to moderate established colitis. Thus, 'no obvious phenotype in vivo' is supported only for the unperturbed mice, not as a general statement about Treg function in vivo. (LLM, conf=0.88)
Experimental — accuracy not yet measuredMice with Dab2 deletion in Treg cells are healthy and do not show phenotypes related to autoimmunity defects even at 1 year of age, indicating that Dab2 is dispensable for Treg cells in maintaining T cell tolerance.
“However, mice with Dab2 deletion in Treg cells are healthy in appearance and do not show phenotypes related to autoimmunity defects even at 1 year of age, indicating that the Dab2 is dispensable for Treg cells in maintaining T cell tolerance (Jain et al., 2009).”
From Endocytosis and Physiology: Insights from Disabled-2 Deficient Mice (2016) · cites this paper as Jain et al., 2009
The Results and Discussion section reports that Dab2-deficient mice appeared healthy and had no overt autoimmunity at 10–12 months, suggesting that their Treg cells maintained naïve T cell tolerance. The claim omits that qualifier: the same section reports that Dab2-deficient Treg cells failed to control established colitis, so the paper does not establish that Dab2 is dispensable for Treg-mediated tolerance generally. Page numbers are not provided in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredDab2 null Treg cells fail to suppress T cells.
“Immune system/Treg | No obvious phenotype in vivo; failed to suppress T cells”
From Endocytosis and Physiology: Insights from Disabled-2 Deficient Mice (2016) · cites this paper as Jain et al., 2009
Dab2-deficient Treg cells failed to alleviate established colitis, suggesting a role of Dab2 in regulating lymphocyte infiltration and accumulation in the colon.
“In additional analysis, it was observed that Dab2-deficient Treg cells failed to alleviate established colitis, suggesting a role of Dab2 in regulating lymphocyte infiltration and accumulation in the colon.”
From Endocytosis and Physiology: Insights from Disabled-2 Deficient Mice (2016) · cites this paper as Jain et al., 2009
Dab2 gene deletion was reported to affect regulatory T cell (Treg) function.
“Dab2 gene deletion was reported to affect regulatory T cell (Treg) function (Jain et al., 2009).”
From Endocytosis and Physiology: Insights from Disabled-2 Deficient Mice (2016) · cites this paper as Jain et al., 2009
Dab2-deficient Treg cells are poor suppressors in vitro due to a deficiency in gap junctions for transferring cAMP to effector T cells, because of a role for Dab2 in endocytic trafficking of connexins, components of the gap junctions.
“A mechanism was suggested that the Dab2-deficient Treg cells are poor suppressors in vitro due to a deficiency in gap junctions for transferring cAMP to effector T cells, because of a role for Dab2 in endocytic trafficking of connexins, components of the gap junctions (Jain et al., 2009).”
From Endocytosis and Physiology: Insights from Disabled-2 Deficient Mice (2016) · cites this paper as Jain et al., 2009
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Research works printed but not linked: 23
- 2003, Control of regulatory T cell development by the transcription factor Foxp3., 1057
- 2001, The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3., 20
- 2007, Foxp3-dependent programme of regulatory T-cell differentiation., 771
- 2008, CTLA-4 control over Foxp3+ regulatory T cell function., 271
- 2009, CD4+ regulatory T cells require CTLA-4 for the maintenance of systemic tolerance., 421
- 2006, FOXP3 controls regulatory T cell function through cooperation with NFAT., 375
- 2007, The inhibitory cytokine IL-35 contributes to regulatory T-cell function., 566
- 2009, Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein., 80
- 2001, The adaptor molecule Disabled-2 links the transforming growth factor β receptors to the Smad pathway., 2789
- 2005, Disabled-2 (Dab2) is required for transforming growth factor β-induced epithelial to mesenchymal transition (EMT)., 17540
- 2007, Internalization of large double-membrane intercellular vesicles by a clathrin-dependent endocytic process., 337
- 2001, Disabled-2 colocalizes with the LDLR in clathrin-coated pits and interacts with AP-2., 111
- 1999, Differential expression of mouse Disabled 2 gene in retinoic acid-treated F9 embryonal carcinoma cells and early mouse embryos., 179
- 2003, Conversion of peripheral CD4+CD25− naive T cells to CD4+CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3., 1875
- 2007, Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid., 256
- 2002, Dual roles for the Dab2 adaptor protein in embryonic development and kidney transport., 1555
- 2001, A critical role for Dnmt1 and DNA methylation in T cell development, function, and survival., 763
- 2006, Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells., 235
- 2003, Colitogenic Th1 cells are present in the antigen-experienced T cell pool in normal mice: control by CD4+ regulatory T cells and IL-10., 971
- 2007, Cyclic adenosine monophosphate is a key component of regulatory T cell-mediated suppression., 1303
- 2006, Regulatory T cells suppress systemic and mucosal immune activation to control intestinal inflammation., 256
- 2007, TGFβ signalling in control of T-cell-mediated self-reactivity., 443
- 2007, Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature., 786
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Endocytosis and Physiology: Insights from Disabled-2 Deficient Mice
Tao, W., Moore, R., Smith, E. R., & Xu, X.-X. (2016) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2016.00129 · Cited by 43
Metadata
- Authors
- Jain, N., Nguyen, H., Friedline, R. H., Malhotra, N., Brehm, M., Koyanagi, M., Bix, M., Cooper, J. A., Chambers, C. A., & Kang, J.
- Affiliations
- Department of Pathology, Graduate Program in Immunology and Virology, University of Massachusetts Medical School , Worcester, MA 01655
- Department of Immunology, St. Jude Children’s Research Hospital , Memphis, TN 38105
- Division of Basic Sciences, Fred Hutchinson Cancer Research Center , Seattle, WA 98109
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-10-01
- Volume
- 183
- Issue
- 7
- Pages
- 4192-4196
- ISSN
- 1550-6606
- 0022-1767
- PMC
- PMC2852251
- Cited by
- 31
- References
- 0
- Language
- en
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