Expression and function of toll-like receptors in peripheral blood mononuclear cells of patients with polymyalgia rheumatica and giant cell arteritis

Abstract

These data suggest activation of TLR7 during the active phase of PMR and GCA which resolves with complete disease remission. Whether this finding is the consequence of the marked inflammatory process in these disorders or activation by natural ligands remains to be explored.

Phagocyte dysfunction in polymyalgia rheumatica and other age-related, chronic, inflammatory conditions

“…However, it is possible that there are other aspects of monocyte function, such as NO production [54], as previously demonstrated in GCA lesions. Moreover, increased production of inflammatory cytokines by tissue macrophages and circulating monocytes has been shown in GCA and PMR [53,55]. We did not investigate these aspects.…”

“…TLRs can also be involved in the increased phagocytic ability of circulating neutrophils, as shown in our patients with GCA. In this regard, we have previously shown deregulation in the expression and function of TLRs in peripheral blood monocytes [53]. TLR7 expression is clearly increased in circulating monocytes of patients with active GCA, but its function is impaired, as determined by cytokine production.…”

New insights into the pathogenesis of giant cell arteritis

“…Experiments performed in a mice model in which temporal arteries were subcutaneously engrafted into SCID mice have shown that allogeneic T cells do not recognize engrafted human arteries unless the immune privilege of the arterial wall has been broken by the activation of TLR4 with lipopolysaccharides [61]. Patients with GCA have altered TLR functions as demonstrated by the decrease TLR7 response during the acute phase of the disease [60] and the increased expression of TLR2 and TLR4 on arterial DCs [62]. TLR4-mediated DCs stimulation markedly enhances production of the chemokine CCL20, inducing the recruitment of CCL20-responsive CCR6 + T cells that dominate the vasculitic infiltrates in patients with panarteritic GCA (Fig.…”

“…DCs, lymphocytes and macrophages are the predominant cellular components of the inflammatory infiltrate in affected vessels and also frequently contain multinucleated giant cells [10]. It has been historically proposed that the initiating immunological event is the activation of adventitial dendritic cells through the activation of TLRs [60]. Activation of diverse TLRs induces distinct cytokine/chemokine profiles that might responsible for the loss of arterial immune-privilege [60].…”

“…It has been historically proposed that the initiating immunological event is the activation of adventitial dendritic cells through the activation of TLRs [60]. Activation of diverse TLRs induces distinct cytokine/chemokine profiles that might responsible for the loss of arterial immune-privilege [60]. Experiments performed in a mice model in which temporal arteries were subcutaneously engrafted into SCID mice have shown that allogeneic T cells do not recognize engrafted human arteries unless the immune privilege of the arterial wall has been broken by the activation of TLR4 with lipopolysaccharides [61].…”