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

Noah Alberts-Grill, Daniel Engelbertsen, Dexiu Bu, Amanda Foks, Nir Grabie, Jan M. Herter, Felicia Kuperwaser, Tao Chen, Gina Destefano, Petr Jarolim, Andrew H. Lichtman

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

9 Citeringar (SciVal)

Sammanfattning

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.

Originalspråkengelska
Sidor (från-till)4651-4662
TidskriftJournal of Immunology
Volym197
Utgåva12
DOI
StatusPublished - 2016 dec. 15
Externt publiceradJa

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