Cellular Signaling Pathways in Medium and Large Vessel Vasculitis

Frontiers in Immunology

Ryu Watanabe¹  David H. Liang¹  Jörg J. Goronzy¹  Cornelia M. Weyand¹  Gerald J. Berry² 

[1] Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States;Department of Pathology, Stanford University School of Medicine, Stanford, CA, United States;

关键词: giant cell arteritis;    Takayasu arteritis;    large vessel vasculitis;    T cells;    macrophages;    NOTCH;   

DOI  :  10.3389/fimmu.2020.587089

来源: DOAJ

【 摘 要 】

Autoimmune and autoinflammatory diseases of the medium and large arteries, including the aorta, cause life-threatening complications due to vessel wall destruction but also by wall remodeling, such as the formation of wall-penetrating microvessels and lumen-stenosing neointima. The two most frequent large vessel vasculitides, giant cell arteritis (GCA) and Takayasu arteritis (TAK), are HLA-associated diseases, strongly suggestive for a critical role of T cells and antigen recognition in disease pathogenesis. Recent studies have revealed a growing spectrum of effector functions through which T cells participate in the immunopathology of GCA and TAK; causing the disease-specific patterning of pathology and clinical outcome. Core pathogenic features of disease-relevant T cells rely on the interaction with endothelial cells, dendritic cells and macrophages and lead to vessel wall invasion, formation of tissue-damaging granulomatous infiltrates and induction of the name-giving multinucleated giant cells. Besides antigen, pathogenic T cells encounter danger signals in their immediate microenvironment that they translate into disease-relevant effector functions. Decisive signaling pathways, such as the AKT pathway, the NOTCH pathway, and the JAK/STAT pathway modify antigen-induced T cell activation and emerge as promising therapeutic targets to halt disease progression and, eventually, reset the immune system to reestablish the immune privilege of the arterial wall.

【 授权许可】

Unknown