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Aberrant distribution and function of plasmacytoid dendritic cells in patients with ankylosing spondylitis are associated with unfolded protein response.
- Source :
-
The Kaohsiung journal of medical sciences [Kaohsiung J Med Sci] 2020 Jun; Vol. 36 (6), pp. 441-449. Date of Electronic Publication: 2020 Jan 21. - Publication Year :
- 2020
-
Abstract
- Although human leucocyte antigen (HLA)-B27 is strongly associated with ankylosing spondylitis (AS), the association of unfolded protein response (UPR) induced by HLA-B27 misfolding in AS remains controversial. Since dendritic cells (DCs) are crucial in induction of AS in HLA-B27-transgenic rats, and plasmacytoid DCs (pDCs) belong to one type of DCs, we here aim to study the relevance of pDCs and UPR in AS. Peripheral pDCs were isolated from 27 HLA-B27(+) AS patients and 37 controls. The bone marrow (BM) and synovium of inflamed hips from AS patients and controls were obtained. We found a significantly higher frequency of pDCs in the peripheral blood, BM, or inflamed synovium of hips, which is associated with the enhanced expression of pDC trafficking molecules, CCR6 and CCL20 in the synovium of AS patients. Functional analysis further revealed that several inflammatory cytokines, including TNFα, IL-6, and IL-23, secreted by pDCs were significantly increased in AS patients as compared with those in controls. Remarkably, protein kinase RNA-like endoplasmic reticulum kinase (PERK) pathway in UPR was up-regulated in pDCs of AS patients. Notably, PERK inhibitor treatment significantly inhibited the enhanced cytokine production by pDCs of AS patients. Further, the extent of PERK activation was significantly associated with the increased disease severity of AS patients. Our data uncover the aberrant distribution and function of pDCs in AS patients. The up-regulated PERK pathway in UPR of pDCs not only contributes to enhanced cytokine production of pDCs, but also is associated with increased disease activity of AS patients.<br /> (© 2020 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.)
- Subjects :
- Adenine analogs & derivatives
Adenine pharmacology
Bone Marrow Cells immunology
Bone Marrow Cells pathology
Case-Control Studies
Cell Count
Chemokine CCL20 genetics
Chemokine CCL20 immunology
Dendritic Cells pathology
HLA-B27 Antigen immunology
Hip
Humans
Immunophenotyping
Indoles pharmacology
Interleukin-23 genetics
Interleukin-23 immunology
Interleukin-6 genetics
Interleukin-6 immunology
Protein Kinase Inhibitors pharmacology
Receptors, CCR6 genetics
Receptors, CCR6 immunology
Severity of Illness Index
Signal Transduction
Spondylitis, Ankylosing genetics
Spondylitis, Ankylosing pathology
Synovial Membrane immunology
Synovial Membrane pathology
Tumor Necrosis Factor-alpha genetics
Tumor Necrosis Factor-alpha immunology
eIF-2 Kinase antagonists & inhibitors
eIF-2 Kinase immunology
Dendritic Cells immunology
HLA-B27 Antigen genetics
Spondylitis, Ankylosing immunology
Unfolded Protein Response
eIF-2 Kinase genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2410-8650
- Volume :
- 36
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Kaohsiung journal of medical sciences
- Publication Type :
- Academic Journal
- Accession number :
- 31961055
- Full Text :
- https://doi.org/10.1002/kjm2.12184