Distinct Role Of Plasmacytoid Dendritic Cells and Mast Cells In The Pathogenesis Of Sjӧgren’s Syndrome

Jidong Zhao¹, Kunihiro Yamaoka¹, Satoshi Kubo¹, Shingo Nakayamada² and Yoshiya Tanaka¹, ¹The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan, ²First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan

Meeting: ACR/ARHP Annual Meeting 2013

Keywords: Dendritic cells, histopathologic and mast cells, Sjogren's syndrome

Session Information

Title: Sjögren's Syndrome: Basic Science

Session Type: Abstract Submissions (ACR)

Background/Purpose:

Sjögren’s Syndrome (SS) is characterized by the destruction of the lacrimal and salivary grands due to autoreactive lymphocyte infiltration in the early phase and subsequent intralobular fibrosis and acinar atrophy at late phase of the disease. Involvement of plasmacytoid dendritic cells (pDCs) and mast cells (MCs) has been suggested, although their detailed role in pathology is poorly understood. The aim of this study was to investigate the role pDCs and MCs in the disease course of SS.

Methods:

Lip biopsy specimen from 178 SS patients and 7 Sicca syndrome (Sicca) patients were analyzed. NanoZoomer Digital Pathology (NDP), a system to convert a histology slide into high-resolution digital slides and enables sequential pathological analysis of multiple sections and measurement of accurate specimen area was utilized for analysis. Density of pDCs and MCs (/mm²) was measured with NDP and histological scoring was performed on lymphocytes infiltration, acinar atrophy and intralobular fibrosis. pDC, CXCL13 and CD68 were detected by immunohistochemistry and MCs were detected by toluidine blue staining. Histological stage was based on ‘Greenspan grade’.

Results: Significant lymphocytes infiltration, acinar atrophy and intralobular fibrosis were observed in SS compared to Sicca patients with salivary gland destruction. Both, pDCs and MCs were significantly increased in SS compared to Sicca (12.6±10.2 vs 3.4±3.7, 43.7±21.8 vs 21.5±6.9). Positive correlation between density of pDCs with lymphocytes infiltration score (p��0.02) and density of MCs with intralobular fibrosis score (p��0.03) was observed in primary SS but not in secondary SS. Moreover, in the primary SS, density of CXCL13 positive infiltrating cells positively correlated with the degree of lymphocyte infiltration score and density of pDCs (p<0.001); by double immunostaining of anti-CXCL13 and anti-CD68, we found that most of CXCL13 positive infiltrating cells are from Macrophage(57.8±22.1%) and the localization of PDC and CXCL13 positive infiltrating cells are almost same around duct. On the other hand, no correlation was observed with secondary SS patients.

Conclusion: Our data suggests the specific role of pDCs in lymphocyte infiltration in primary SS. Correlation of CXCL13 expression, a chemoattractant for lymphocyte recruitement, with lymphocyte infiltration and density of pDCs further suggests the important role of pDCs. CXCL13 is induced by type1 IFN, whereas pDCs are the major source of type 1 IFN. Therefore, it likely that type 1 IFN produced by pDCs in the early stage of the disease induces CXCL13 production of infiltrating cells, especially Macrophage, contributing to lymphocyte infiltration constructing germinal center. In addition, MCs seems to be involved in intralobular fibrosis which occurs in the mid to late stage of SS.

Disclosure:

J. Zhao,
None;

K. Yamaoka,
None;

S. Kubo,
None;

S. Nakayamada,
None;

Y. Tanaka,
None.

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