Cellular Signaling Pathways in Medium and Large Vessel Vasculitis

Ryu Watanabe, Gerald J. Berry, David H. Liang, Jörg J. Goronzy, Cornelia M. Weyand

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number587089
JournalFrontiers in immunology
Volume11
DOIs
StatePublished - Sep 25 2020

Keywords

  • NOTCH
  • T cells
  • Takayasu arteritis
  • co-stimulation
  • giant cell arteritis
  • immune checkpoint
  • large vessel vasculitis
  • macrophages

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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