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Distribution of Myeloid Dendritic Cells and Plasmacytoid Dendritic Cells in the Synovial Tissues of Rheumatoid Arthritis

YUYA TAKAKUBO, MICHIAKI TAKAGI, KUNIHIKO MAEDA, YASUNOBU TAMAKI, AKIKO SASAKI, TAMON ASANO, SHIGENOBU FUKUSHIMA, YOSHIRO KIYOSHIGE, HIROSHI ORUI, TOSHIHIKO OGINO, and MITSUNORI YAMAKAWA

ABSTRACT.

Objective.
To examine the precise tissue distribution of dendritic cells (DC) and indoleamine 2,3-dioxygenase (IDO)-expressing cells in synovial tissue and synovial fluid (SF) from patients with rheumatoid arthritis (RA) and osteoarthritis (OA).

Methods. Synovial tissues from 30 patients with RA and 7 with OA were immunohistochemically stained for DC markers. The examined areas were classified into 5 categories based on pathobiological staging and histopathological grading systems. Myeloid DC (mDC) and plasmacytoid DC (pDC) were isolated using positive and negative magnetic sorting systems, respectively, from SF samples (7 patients with RA and 4 with OA) and synovial tissues (3 RA, 4 OA).

Results. mDC were mainly observed in lymphoid aggregations. pDC were scattered around perivenular infiltration areas, and small and large lymphoid aggregations in RA. The mDC/pDC ratio increased significantly, with higher grading in RA SF tissues compared to OA synovial tissues (p < 0.05). IDO-immunoreactivity was detected in pDC by serial sectioning and staining of RA synovial tissues.

Conclusion. Our results indicate that mature mDC play a central role in the RA inflammatory process. Although there were fewer pDC than mDC, the presence of IDO-positive pDC suggests a possible tolerance mechanism in RA synovial tissues. However, it is probably modest due to the marked inflammation in RA, in which mDC are dominant. (J Rheumatol First Release Sept 1 2008)

Key Indexing Terms:

DENDRITIC CELLS
RHEUMATOID ARTHRITIS
SYNOVIAL TISSUE
DISTRIBUTION
INDOLEAMINE 2,3-DIOXYGENASE


From the Departments of Orthopaedic Surgery and Pathology, Yamagata University School of Medicine; and Yamagata Saisei Hospital, Yamagata, Japan.

Y. Takakubo, MD, PhD, Departments of Orthopaedic Surgery and Pathology; M. Takagi, MD, PhD, Department of Orthopaedic Surgery; K. Maeda, MD, PhD, Department of Pathology; Y. Tamaki, MD, PhD; A. Sasaki, MD, PhD; T. Asano, MD; S. Fukushima, MD, Department of Orthopaedic Surgery, Yamagata University School of Medicine; Y. Kiyoshige, MD, PhD, Yamagata Saisei Hospital; H. Orui, MD, PhD; T. Ogino, MD, PhD, Department of Orthopaedic Surgery; M. Yamakawa, MD, PhD, Department of Pathology, Yamagata University School of Medicine.

Address reprint requests to Dr. Y. Takakubo, Department of Orthopaedic Surgery, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, Japan. E-mail: takakubo-y@med.id.yamagata-u.ac.jp

Accepted for publication May 20, 2008.



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