Dendritic cell KLF2 expression regulates T cell activation and proatherogenic immune responses
(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.
(Less)
- author
- publishing date
- 2016-12-15
- 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
-
- scopus:85002187755
- pmid:27837103
- 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
- 2024-10-02 21:09:34
@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}}, }