Dirk Lievens and colleagues have reported an important finding that contributes to our understanding of the role of transforming growth factor β (TGF-β) in atherosclerotic plaque formation. The work has been published in the European Heart Journal.
The IPEK scientists investigated the effects of TGF-β signaling in dendritic cells by the use of ApoE-/-CD11c-dnTGFβRII (Apoe-/-CD11cDNR) transgenic mice. Blocking TGF-β signaling in CD11c positive cells accelerated the development of atherosclerosis in ApoE deficient mice and induced the development of lesions with increased inflammation and decreased collagen content. In addition, TGF-β signaling in CD11c expressing cells showed to play a key role in the regulation of the activation of T-cells during atherogenesis. More specific, the data suggest that TGF-β signaling in CD11c cells provides a first inhibitory link between the innate and adaptive immune response and indirectly modulates adaptive immune responses by inhibiting DCs from the innate immune system to prime T-cells towards an effector T-cell phenotype.
The significance of the work by Lievens et al. is underlined by an editorial from Klaus Ley and Kevin Tse. Pubmed
|
Group (year) |
Experiment |
Plaque Area |
Plaque Inflammation |
Plaque Fibrosis |
Induced Cytokines |
|
Mallat
(2001)
|
Abs against TGF-ß1, TGF-ß2 and TGF-ß3 ApoE-/- acceptor mice
|
+
|
+
|
-
|
|
|
Lutgens
(2002)
|
rs TGFßRII ApoE-/- acceptor mice
|
-
|
+
|
-
|
|
|
Robertson
(2003)
|
CD4-dnTGFßRII tg+ ApoE-/- background
|
+
|
+
|
-
|
>IFN-gamma >TNF-alpha >IL-4,5,10 |
|
Gojova
(2003)
|
CD2-dnTGFßRII tg+ BMT in LDLr-/- mice
|
-
|
+
|
-
|
>IFN-gamma >IL4,5 |
|
Frutkin
(2009)
|
Cardiac specific TGF-ß overexpression ApoE-/- background
|
-
|
-
|
+
|
<IFN-gamma <TNF-alpha <MIP1-alpha |
|
Lievens
(2012)
|
CD11c-dnTGFßRII tg+ ApoE-/- background
|
+
|
+
|
-
|
>IFN-gamma >TNF-alpha >IL4,10,17 |
Table: Overview of studies on the effects of TGF-ß signaling in atherosclerosis, with focus on plaque area, plaque phenotype and the induced cytokines. (BMT: Bone Marrow Transplantation; +: increase; - : decrease).
Publication:
Abrogated transforming growth factor beta receptor II (TGFβRII) signalling in dendritic cells promotes immune reactivity of T cells resulting in enhanced atherosclerosis. Lievens D, Habets KL, Robertson AK, Laouar Y, Winkels H, Rademakers T, Beckers L, Wijnands E, Boon L, Mosaheb M, Ait-Oufella H, Mallat Z, Flavell RA, Rudling M, Binder CJ, Gerdes N, Biessen EA, Weber C, Daemen MJ, Kuiper J, Lutgens E. Eur Heart J. 2012 May 21. Pubmed
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