Phenotype of Resting and Activated Monocyte-Derived Dendritic Cells Grown from Peripheral Blood of Patients with Ankylosing Spondylitis

Abstract

Decreased levels of class II major histocompatibility complex (MHC) expression and impaired formation of immunological synapse by dendritic cells (DCs) of HLA-B27 transgenic rats have been recently demonstrated. The resulting dysfunction of DCs may be implicated in the pathogenesis of the HLA-B27-related disease in transgenic animals. The phenotype of DCs in patients with ankylosing spondylitis (AS) has not been evaluated. Monocyte-derived DCs (MDDCs) were grown from patients with active AS and age-matched healthy volunteers. Surface expression of HLA-DR, co-stimulation molecules CD80, CD86 and CD40, as well as CD83 was assessed by flow cytometry and compared between the groups under 3 conditions: in resting state, after stimulation by lipopolysaccharide (LPS) and after stimulation by LPS in the presence of etanercept, a soluble receptor of tumor necrosis factor α. Lower baseline expression of class II MHC molecules (HLA-DR) was observed by MDDCs grown from AS patients, as compared to healthy subjects. Post-stimulated levels of HLA-DR were comparable in both groups, suggesting greater up-regulation of class II MHC molecules by MDDCs from AS in response to LPS. No difference between groups in the levels of expression of co-stimulation molecules and CD83 was observed. Lower basic expression of class II MHC by the MDDCs grown from patients with AS may be associated with impaired regulation of their activity. Functional studies on DCs from patients with AS are needed to evaluate the integrity of their antigen-presenting function.

Ankylosing spondylitis patients display altered dendritic cell and T cell populations that implicate pathogenic roles for the IL-23 cytokine axis and intestinal inflammation

“…Despite this, evidence for IL-17–secreting T cells in inflamed, extra-articular tissues is limited [ 26–28 ]. Furthermore, examination of the critical myeloid populations has only been performed indirectly, using in vitro -generated mo-DCs [ 15 , 16 ]. These cultures do not recapitulate the diverse populations found in vivo .…”

“…Most have heretofore focused on cells generated from monocytes following ex vivo culture with GM-CSF and IL-4 (mo-DCs) [ 14 ]. These express reduced surface MHC II expression compared with cells from healthy individuals, but no alteration in production of IL-23 or other cytokines [ 15 , 16 ]. On the other hand, in vitro studies do suggest that ER stress of DCs could lead to excessive IL-23 production [ 17 ], and as such they are intriguing candidate cells in initiating this effector pathway.…”

The Potential Role of Genetics, Environmental Factors, and Gut Dysbiosis in the Aberrant Non-Coding RNA Expression to Mediate Inflammation and Osteoclastogenic/Osteogenic Differentiation in Ankylosing Spondylitis

“…The adaptive immune cells include helper T, Treg, CD8 + T, and B cells ( Rezaiemanesh, et al, 2018 ). Much evidence has demonstrated that certain phenotypes of resting and activated macrophages expressing scavenger receptor, CD163, can link between immune alterations of the gut and synovial inflammation in AS ( Baeten et al, 2002 ; Slobodin et al, 2012 ; Talpin et al, 2014 ; Wright et al, 2016 ; Rezaiemanesh et al, 2017 ). The abnormal polarization of macrophages induced by IL-4 was found in AS patients ( Lin et al, 2015 ).…”

Spondyloarthritides: Theories and beyond

“…The level of circulating CD141+ dendritic cells (DCs) show a positive correlation with BASDAI in AS patients (53). Moreover, lower levels of MHC class II expression in DCs of AS patients (54) and animal model (55) implies that distortions in antigen presentation might very well be a key factor in disease pathogenesis.…”