Aberrant Distribution and Function of Plasmacytoid Dendritic Cells in Patients with Ankylosing Spondylitis Are Associated with Unfolded Protein Response

Liu Chin-Hsiu¹, Chen Chun-Hsiung¹ and Lin Kuo-I², ¹Division of Allergy, Immunology and Rheumatology, Division of Allergy, Immunology and Rheumatology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taiwan., New Taipei city, Taiwan, ²Genomics Research Center, Academia Sinica, Taipei, Taiwan., Taipei city, Taiwan

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Ankylosing spondylitis (AS) and dendritic cells

Session Information

Date: Tuesday, October 23, 2018

Title: Spondyloarthritis Including Psoriatic Arthritis – Basic Science Poster

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Although human leukcocyte antigen (HLA)-B27 is strongly associated with ankylosing spondylitis (AS) and HLA-B27 misfolding induces unfolded protein response (UPR), whether UPR is associated with AS remains controversial. It has been speculated that UPR might occur in more specific immune cells. Since dendritic cells (DCs) are crucial in induction and maintenance of AS in HLA-B27-transgenic rat, and plasmacytoid DCs (pDCs) belong to one type of DCs, we here aim to study the relevance of plasmacytoid DCs (pDCs) in AS and explore if UPR in pDCs contributes to the pathogenesis of AS.

Methods: Peripheral pDCs were isolated from 43 AS patients and 39 controls. The bone marrow (BM) and synovium of inflamed hips from AS patients and controls were obtained. Functional and phenotypic analyses of pDCs and their relationship with UPR was investigated.

Results: We found a significantly higher frequency of pDCs in the peripheral blood, BM and inflamed synovium of hips in AS patients. Functional analysis further revealed that the inflammatory cytokines secreted by isolated peripheral pDCs were significantly increased in AS patients compared with those in normal controls. Remarkably, binding immunoglobulin protein (BIP) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) pathway in UPR were up-regulated in unstimulated pDCs of AS patients. Of note, PERK inhibitor treatment significantly inhibited the enhanced cytokine production by pDCs isolated from peripheral blood of AS patients. Furthermore, the extent of PERK activation was significantly associated with the increased disease severity of AS patients, the increased expression of pDC development marker, FMS-like tyrosine kinase (FLT) 3, and tissue homing marker, chemokine receptor (CCR) 6, of pDCs in AS patients.

Conclusion: Our data uncover that the activation of UPR may occur in pDCs of AS patients. The up-regulated PERK pathway in pDCs not only contributes to the aberrant synovial distribution and enhanced inflammatory function of pDCs in AS patients, but also is associated with systemic disease activity of AS patients.

Disclosure: L. Chin-Hsiu, None; C. Chun-Hsiung, None; L. Kuo-I, None.

To cite this abstract in AMA style:

Chin-Hsiu L, Chun-Hsiung C, Kuo-I L. Aberrant Distribution and Function of Plasmacytoid Dendritic Cells in Patients with Ankylosing Spondylitis Are Associated with Unfolded Protein Response [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/aberrant-distribution-and-function-of-plasmacytoid-dendritic-cells-in-patients-with-ankylosing-spondylitis-are-associated-with-unfolded-protein-response/. Accessed .

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