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Dendritic cell KLF2 expression regulates T cell activation and proatherogenic immune responses

Alberts-Grill, Noah ; Engelbertsen, Daniel LU ; Bu, Dexiu ; Foks, Amanda ; Grabie, Nir ; Herter, Jan M. ; Kuperwaser, Felicia ; Chen, Tao ; Destefano, Gina and Jarolim, Petr , et al. (2016) In Journal of Immunology 197(12). p.4651-4662
Abstract

Dendritic cells (DCs) have been implicated as important regulators of innate and adaptive inflammation in many diseases, including atherosclerosis. However, the molecular mechanisms by which DCs mitigate or promote inflammatory pathogenesis are only partially understood. Previous studies have shown an important anti-inflammatory role for the transcription factor Krüppel-like factor 2 (KLF2) in regulating activation of various cell types that participate in atherosclerotic lesion development, including endothelial cells, macrophages, and T cells. We used a pan-DC, CD11c-specific cre-lox gene knockout mouse model to assess the role of KLF2 in DC activation, function, and control of inflammation in the context of hypercholesterolemia and... (More)

Dendritic cells (DCs) have been implicated as important regulators of innate and adaptive inflammation in many diseases, including atherosclerosis. However, the molecular mechanisms by which DCs mitigate or promote inflammatory pathogenesis are only partially understood. Previous studies have shown an important anti-inflammatory role for the transcription factor Krüppel-like factor 2 (KLF2) in regulating activation of various cell types that participate in atherosclerotic lesion development, including endothelial cells, macrophages, and T cells. We used a pan-DC, CD11c-specific cre-lox gene knockout mouse model to assess the role of KLF2 in DC activation, function, and control of inflammation in the context of hypercholesterolemia and atherosclerosis. We found that KLF2 deficiency enhanced surface expression of costimulatory molecules CD40 and CD86 in DCs and promoted increased T cell proliferation and apoptosis. Transplant of bone marrow from mice with KLF2-deficient DCs into Ldlr-/- mice aggravated atherosclerosis compared with control mice, most likely due to heightened vascular inflammation evidenced by increased DC presence within lesions, enhanced T cell activation and cytokine production, and increased cell death in atherosclerotic lesions. Taken together, these data indicate that KLF2 governs the degree of DC activation and hence the intensity of proatherogenic T cell responses.

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publishing date
type
Contribution to journal
publication status
published
in
Journal of Immunology
volume
197
issue
12
pages
4651 - 4662
publisher
American Association of Immunologists
external identifiers
  • pmid:27837103
  • scopus:85002187755
ISSN
0022-1767
DOI
10.4049/jimmunol.1600206
language
English
LU publication?
no
id
8e59715f-ca4a-4509-a4a4-4e0ac7245189
date added to LUP
2020-02-02 16:55:34
date last changed
2020-08-19 08:41:52
@article{8e59715f-ca4a-4509-a4a4-4e0ac7245189,
  abstract     = {<p>Dendritic cells (DCs) have been implicated as important regulators of innate and adaptive inflammation in many diseases, including atherosclerosis. However, the molecular mechanisms by which DCs mitigate or promote inflammatory pathogenesis are only partially understood. Previous studies have shown an important anti-inflammatory role for the transcription factor Krüppel-like factor 2 (KLF2) in regulating activation of various cell types that participate in atherosclerotic lesion development, including endothelial cells, macrophages, and T cells. We used a pan-DC, CD11c-specific cre-lox gene knockout mouse model to assess the role of KLF2 in DC activation, function, and control of inflammation in the context of hypercholesterolemia and atherosclerosis. We found that KLF2 deficiency enhanced surface expression of costimulatory molecules CD40 and CD86 in DCs and promoted increased T cell proliferation and apoptosis. Transplant of bone marrow from mice with KLF2-deficient DCs into Ldlr<sup>-/-</sup> mice aggravated atherosclerosis compared with control mice, most likely due to heightened vascular inflammation evidenced by increased DC presence within lesions, enhanced T cell activation and cytokine production, and increased cell death in atherosclerotic lesions. Taken together, these data indicate that KLF2 governs the degree of DC activation and hence the intensity of proatherogenic T cell responses.</p>},
  author       = {Alberts-Grill, Noah and Engelbertsen, Daniel and Bu, Dexiu and Foks, Amanda and Grabie, Nir and Herter, Jan M. and Kuperwaser, Felicia and Chen, Tao and Destefano, Gina and Jarolim, Petr and Lichtman, Andrew H.},
  issn         = {0022-1767},
  language     = {eng},
  month        = {12},
  number       = {12},
  pages        = {4651--4662},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Dendritic cell KLF2 expression regulates T cell activation and proatherogenic immune responses},
  url          = {http://dx.doi.org/10.4049/jimmunol.1600206},
  doi          = {10.4049/jimmunol.1600206},
  volume       = {197},
  year         = {2016},
}