Pathogenic role of monocytes/macrophages in large vessel vasculitis

Abstract

Vasculitis is an autoimmune vascular inflammation with an unknown etiology and causes vessel wall destruction. Depending on the size of the blood vessels, it is classified as large, medium, and small vessel vasculitis. A wide variety of immune cells are involved in the pathogenesis of vasculitis. Among these immune cells, monocytes and macrophages are functionally characterized by their capacity for phagocytosis, antigen presentation, and cytokine/chemokine production. After a long debate, recent technological advances have revealed the cellular origin of tissue macrophages in the vessel wall. Tissue macrophages are mainly derived from embryonic progenitor cells under homeostatic conditions, whereas bone marrow-derived circulating monocytes are recruited under inflammatory conditions, and then differentiate into macrophages in the arterial wall. Such macrophages infiltrate into an otherwise immunoprotected vascular site, digest tissue matrix with abundant proteolytic enzymes, and further recruit inflammatory cells through cytokine/chemokine production. In this way, macrophages amplify the inflammatory cascade and eventually cause tissue destruction. Recent studies have also demonstrated that monocytes/macrophages can be divided into several subpopulations based on the cell surface markers and gene expression. In this review, the subpopulations of circulating monocytes and the ontogeny of tissue macrophages in the artery are discussed. We also update the immunopathology of large vessel vasculitis, with a special focus on giant cell arteritis, and outline how monocytes/macrophages participate in the disease process of vascular inflammation. Finally, we discuss limitations of the current research and provide future research perspectives, particularly in humans. Through these processes, we explore the possibility of therapeutic strategies targeting monocytes/macrophages in vasculitis.

Changes in the molecular profiles of large-vessel vasculitis treated with biological disease-modifying anti-rheumatic drugs and Janus kinase inhibitors

“…Studies in IL-1Ra-deficient mice also support the association between TNF-α and TAK progression, as the mice exhibited significantly reduced aortitis and arthritis in the absence of TNF-α ( 32 , 33 ). TNF-α acts in conjunction with IFN-γ to stimulate macrophages and induce the production of monocyte chemotactic proteins, particularly CCL2, which recruits monocytes expressing CCR2 to form multinucleated giant cells that are characteristic of LVV ( 26 , 27 , 54 – 56 ). Elevated CCL2 serum levels after treatment with GC suggest that CCL2 may contribute to treatment failure in LVV ( 57 ).…”

Philadelphia chromosome-negative myeloproliferative chronic neoplasms: is clonal hematopoiesis the main determinant of autoimmune and cardio-vascular manifestations?

“…The order of acquisition, whether it occurs first or after other mutations, is crucial. When TET2 mutation is acquired before JAK2 mutation, the thrombotic risk is higher (101).…”

The role of immune aging in Giant Cell Arteritis

“…With progressive age macrophage function decreases resulting in reduced phagocytosis and also an increase in the production of inflammatory cytokines contributing to inflammaging [32]. In GCA, macrophages, specifically multinucleated giant cells are the principal constituent of the granulomatous lesion reflecting their integral role in GCA pathobiology [33]. There are a number of shared similarities between the myeloid cell dysfunction observed in GCA patients and that seen with immune aging.…”