Immune checkpoints in autoimmune vasculitis

Best Pract Res Clin Rheumatol. 2024 Apr 9:101943. doi: 10.1016/j.berh.2024.101943. Online ahead of print.ABSTRACTGiant cell arteritis (GCA) is a prototypic autoimmune disease with a highly selective tissue tropism for medium and large arteries. Extravascular GCA manifests with intense systemic inflammation and polymyalgia rheumatica; vascular GCA results in vessel wall damage and stenosis, causing tissue ischemia. Typical granulomatous infiltrates in affected arteries are composed of CD4+ T cells and hyperactivated macrophages, signifying the involvement of the innate and adaptive immune system. Lesional CD4+ T cells undergo antigen-dependent clonal expansion, but antigen-nonspecific pathways ultimately control the intensity and duration of pathogenic immunity. Patient-derived CD4+ T cells receive strong co-stimulatory signals through the NOTCH1 receptor and the CD28/CD80-CD86 pathway. In parallel, co-inhibitory signals, designed to dampen overshooting T cell immunity, are defective, leaving CD4+ T cells unopposed and capable of supporting long-lasting and inappropriate immune responses. Based on recent data, two inhibitory checkpoints are defective in GCA: the Programmed death-1 (PD-1)/Programmed cell death ligand 1 (PD-L1) checkpoint and the CD96/CD155 checkpoint, giving rise to the "lost inhibition concept". Subcellular and molecular analysis has demonstrated trapping of the checkpoint ligands in the endoplasmic reticulum, creating PD-L1low CD155low antigen-presenting cell...
Source: Cancer Control - Category: Cancer & Oncology Authors: Source Type: research