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Vascular dendritic cells in giant cell arteritis
Cornelia M Weyand1, Wei Ma-Krupa, Olga Pryshchep
1Kathleen B. and Mason I. Lowance Center for Human Immunology, Emory University School of Medicine, Rm. 1003, Woodruff Memorial Research Bldg., 101 Woodruff Cir., Atlanta, GA 30322, USA. cweyand@emory.edu
Annals of the New York Academy of Sciences
|February 8, 2006
Summary
Adventitial dendritic cells (DCs) in the arterial wall can initiate giant cell arteritis (GCA) by becoming activated. This activation leads to T-cell recruitment and inflammation, highlighting DCs as key players in vasculitis.
Area of Science:
- Immunology
- Vascular Biology
- Pathology
Background:
- Giant cell arteritis (GCA) is a vasculitis affecting large arteries, driven by adaptive immune responses.
- CD4 T cells and interferon gamma are crucial in GCA pathogenesis.
- Adventitial dendritic cells (DCs) in the arterial wall are implicated in initiating vasculitis.
Purpose of the Study:
- To investigate the immune effector functions of adventitial DCs in vasculitis initiation.
- To examine the role of Toll-like receptor (TLR) ligands in DC activation and T-cell responses within the arterial wall.
Main Methods:
- Utilized human artery-severe combined immunodeficient (SCID) mouse chimeras.
- Administered TLR2 or TLR4 ligands to induce DC activation.
- Analyzed DC differentiation, T-cell recruitment, and activation markers (CD83, CD86, IL-18).
- Investigated the effects of antibody-mediated DC depletion in established vasculitis.
Main Results:
- Constitutive adventitial DCs are nonstimulatory to T cells.
- TLR ligand triggering induces DC activation, T-cell recruitment, and retention in the arterial wall.
- Activated DCs differentiate into chemokine-producing effector cells expressing CD83 and CD86, mediating T-cell regulation via IL-18.
- DC depletion significantly reduces T-cell and macrophage activation, demonstrating anti-inflammatory effects.
Conclusions:
- Adventitial DCs are responsive to pathogen signals and act as gatekeepers for T-cell responses in the arterial adventitia.
- The switch of adventitial DCs from a nonstimulatory to an activating state is a critical event in initiating vasculitis.
- Targeting adventitial DCs may offer a therapeutic strategy for GCA and other vasculitides.