The Contribution of Innate Immunity in Large-Vessel Vasculitis: Detangling New Pathomechanisms beyond the Onset of Vascular Inflammation

Abstract

Large-vessel vasculitis (LVV) are autoimmune and autoinflammatory diseases focused on vascular inflammation. The central core of the intricate immunological and molecular network resides in the disruption of the “privileged immune state” of the arterial wall. The outbreak, initially primed by dendritic cells (DC), is then continuously powered in a feed-forward loop by the intimate cooperation between innate and adaptive immunity. If the role of adaptive immunity has been largely elucidated, knowledge of the critical function of innate immunity in LVV is still fragile. A growing body of evidence has strengthened the active role of innate immunity players and their key signaling pathways in orchestrating the complex pathomechanisms underlying LVV. Besides DC, macrophages are crucial culprits in LVV development and participate across all phases of vascular inflammation, culminating in vessel wall remodeling. In recent years, the variety of potential pathogenic actors has expanded to include neutrophils, mast cells, and soluble mediators, including the complement system. Interestingly, new insights have recently linked the inflammasome to vascular inflammation, paving the way for its potential pathogenic role in LVV. Overall, these observations encourage a new conceptual approach that includes a more in-depth study of innate immunity pathways in LVV to guide future targeted therapies.

Ultrasound Examination of Common Carotid Adventitial Thickness Can Differentiate Takayasu Arteritis and Large Vessel Giant Cell Arteritis

“…Previous studies have analyzed immunological cellular activation and cytokines production in LVV [ 38 , 39 , 40 ], and others have studied the cause of the preponderance fibrous adventitial reaction in TAK patients. IL-6 production [ 41 ], activation of monocyte/macrophage lineage [ 42 , 43 , 44 , 45 ], high presence of activated mast cells [ 46 ], activated neutrophils [ 47 ], and the presence of Th17 lymphocyte populations [ 48 , 49 ] all seem to contribute to fibroblast activation and collagen deposition in the adventitial layer. A significant difference between LV-GCA and TAK lies in the composition of the wall-infiltrating immune cell compartment, which in TAK, includes a significant population of CD8+ T cells, a low ratio of CD4/CD8 cells, as well as a higher proportion of natural killer cells, indicating the differences in the inflammatory effector pathway [ 39 ].…”

Takayasu’s Arteritis: A Special Case Report and Review of the Literature

“…Macrophages participate beyond all stages of arterial inflammation, as well as in arterial remodeling [12]. Triggers for this autoimmune disorder can be tuberculosis in different locations [13].…”

“…Fragments of the affected arteries can reveal the involvement of all layers, including adventitia inflammation, the destruction of media elastic tissue, and neovascularization of the intima and media [ 11 ]. Macrophages participate beyond all stages of arterial inflammation, as well as in arterial remodeling [ 12 ]. Triggers for this autoimmune disorder can be tuberculosis in different locations [ 13 ].…”