CCL17-expressing dendritic cells drive atherosclerosis by restraining regulatory T cell homeostasis in mice.

نویسندگان

  • Christian Weber
  • Svenja Meiler
  • Yvonne Döring
  • Miriam Koch
  • Maik Drechsler
  • Remco T A Megens
  • Zuzanna Rowinska
  • Kiril Bidzhekov
  • Caroline Fecher
  • Eliana Ribechini
  • Marc A M J van Zandvoort
  • Christoph J Binder
  • Ivett Jelinek
  • Mihail Hristov
  • Louis Boon
  • Steffen Jung
  • Thomas Korn
  • Manfred B Lutz
  • Irmgard Förster
  • Martin Zenke
  • Thomas Hieronymus
  • Tobias Junt
  • Alma Zernecke
چکیده

Immune mechanisms are known to control the pathogenesis of atherosclerosis. However, the exact role of DCs, which are essential for priming of immune responses, remains elusive. We have shown here that the DC-derived chemokine CCL17 is present in advanced human and mouse atherosclerosis and that CCL17+ DCs accumulate in atherosclerotic lesions. In atherosclerosis-prone mice, Ccl17 deficiency entailed a reduction of atherosclerosis, which was dependent on Tregs. Expression of CCL17 by DCs limited the expansion of Tregs by restricting their maintenance and precipitated atherosclerosis in a mechanism conferred by T cells. Conversely, a blocking antibody specific for CCL17 expanded Tregs and reduced atheroprogression. Our data identify DC-derived CCL17 as a central regulator of Treg homeostasis, implicate DCs and their effector functions in atherogenesis, and suggest that CCL17 might be a target for vascular therapy.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Commentary: Indoleamine 2,3-Dioxygenase-Expressing Aortic Plasmacytoid Dendritic Cells Protect against Atherosclerosis by Induction of Regulatory T Cells

Plasmacytoid dendritic cells (pDCs) are unique bone-marrow-derived cells that produce large amounts of type I interferon in response to microbial stimulation. Furthermore, pDCs also promote T cell tolerance in sterile-inflammation conditions. However, the immunomodulatory role of aortic pDCs in atherosclerosis has been poorly understood. Here, we identified functional mouse and human pDCs in th...

متن کامل

Compartmentalized Production of CCL17 In Vivo: Strong Inducibility in Peripheral Dendritic Cells Contrasts Selective Absence from the Spleen

Dendritic cells (DCs) * fulfill an important regulatory function at the interface of the innate and adaptive immune system. The thymus and activation-regulated chemokine (TARC/CCL17) is produced by DCs and facilitates the attraction of activated T cells. Using a fluorescence-based in vivo reporter system, we show that CCL17 expression in mice is found in activated Langerhans cells and mature DC...

متن کامل

Compartmentalized Production of CCL17 In Vivo

Dendritic cells (DCs)(*) fulfill an important regulatory function at the interface of the innate and adaptive immune system. The thymus and activation-regulated chemokine (TARC/CCL17) is produced by DCs and facilitates the attraction of activated T cells. Using a fluorescence-based in vivo reporter system, we show that CCL17 expression in mice is found in activated Langerhans cells and mature D...

متن کامل

Distinct Functions of Specialized Dendritic Cell Subsets in Atherosclerosis and the Road Ahead

Atherosclerotic vascular disease is modulated by immune mechanisms. Dendritic cells (DCs) and T cells are present within atherosclerotic lesions and function as central players in the initiation and modulation of adaptive immune responses. In previous years, we have studied the functional contribution of distinct DC subsets in disease development, namely, that of CCL17-expressing DCs as well as...

متن کامل

Listeria Monocytogenes Activated Dendritic Cell Based Vaccine for Prevention of Experimental Tumor in Mice

Background: The use of dendritic cells (DCs) as a cellular adjuvant provides a promis-ing approach in immunotherapy of cancer. It has been demonstrated that Listeria mono-cytogenes activated DCs pulsed ex vivo with tumor antigens trigger a systemic Th1-biased specific immune response and a single dose of this vaccine will cause a consider-able anti tumor immunity. Objective: The present study w...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • The Journal of clinical investigation

دوره 121 7  شماره 

صفحات  -

تاریخ انتشار 2011