Ankylosing spondylitis M-CSF-derived macrophages are undergoing unfolded protein response (UPR) and express higher levels of interleukin-23

Abstract

Objective: Interleukin (IL)-23/IL-17 pathway involves in the pathogenesis of ankylosing spondylitis (AS). The exact mechanism implicated in overexpression of IL-23 and activation of the IL-23/IL-17 axis is not clear. The aim of the study was to clarify whether macrophages of AS patients undergo unfolded protein response (UPR) and secret increased IL-23.

Methods: Peripheral blood monocyte isolated from 10 HLA-B27⁺ patients and five HLA-B27⁺ normal subjects were differentiated to macrophages by macrophage-colony stimulating factor (M-CSF) for seven days. Flow cytometry was used to detect monocyte purity and expression of macrophage markers. Analysis of mRNA expression for HLA-B and B27, UPR-associated proteins (BiP, CHOP, MDG1, and XBP1) and IL-23 was performed by RT-qPCR.

Results: RT-qPCR data showed a significant overexpression of HLA-B27, UPR genes (BiP, CHOP, and XBP1), and IL-23 in M-CSF-derived macrophages from AS patients compared to healthy controls. Increased expression of MDG1 was not significant.

Conclusions: Our data suggest that UPR activation occurs in M-CSF-derived macrophages of AS patients and is accompanied by overexpression of HLA-B27. UPR appears to be associated with overproduction of IL-23 in AS macrophages.

Keywords:

• Ankylosing spondylitis
• HLA-B27
• Interleukin-23
• Macrophage
• Unfolded protein response (UPR)

Conflict of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Funding

None.