Toll-like receptors in giant cell arteritis

Wei Ma-Krupa, Mildred Kwan, Jörg J. Goronzy, Cornelia M. Weyand

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Giant cell arteritis, a primary vasculitis of medium-sized and large arteries, causes vessel occlusion through fast and concentric intimal hyperplasia. Contextual parameters, especially the topography of the arterial wall, have emerged as critical pathogenic elements. Experimental data support the concept that the disease is initiated in the most outer layer of the arterial wall, the adventitia. CD4 T cells are recruited to the adventitia, undergo local activation and subsequently orchestrate macrophage differentiation. T cells and macrophages infiltrate into all wall layers and acquire different effector functions dependent on cues in their immediate microenvironment. The end result is myofibroblastic proliferation, luminal stenosis, and tissue ischemia. Adaptive immune responses in the adventitia are triggered by a population of indigenous dendritic cells (DC) placed at the adventitia-media junction. These arterial DCs have a unique surface receptor profile, including a series of Toll-like receptors (TLR). Responsiveness of such arterial DCs to blood-borne stimuli has been studied in human arteries engrafted into immunodeficient mice. Ligands of TLR4 are able to start maturation of adventitial DCs which fail to leave the peripheral tissue site. Instead, these adventitial DCs produce chemokines, recruit T cells, and support their local activation. These data identify tissue-residing DCs as gatekeepers in vasculitis and support the model that TLR ligands function as instigators of vessel wall inflammation.

Original languageEnglish (US)
Pages (from-to)38-46
Number of pages9
JournalClinical Immunology
Volume115
Issue number1 SPEC. ISS.
DOIs
StatePublished - Apr 2005

Keywords

  • Chemokines
  • Cytokines
  • Dendritic cells
  • Giant cell arteritis
  • T cells
  • Toll-like receptors
  • Vasculitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Toll-like receptors in giant cell arteritis'. Together they form a unique fingerprint.

Cite this