Background/Purpose:

Mast cells have been implicated in many immune-inflammatory disorders. They mediate a variety of inflammatory and fibrotic conditions, but their role in sialadenitis and interstitial lung disease in patients with primary Sjögren syndrome is unclear. We examined whether mast cells play a critical role in the pathogenesis of Sjögren syndrome.

Methods:

Labial salivary glands and lung tissue were examined using histological and immunohistochemistry methods. Labial salivary gland samples were collected from 15 individuals with primary Sjögren syndrome and 7 with sicca syndrome (controls). Saliva production was evaluated by Saxon test.

Affected lung tissue from four patients with Sjögren syndrome-associated interstitial lung disease was obtained via biopsy. As control samples, we used 10 noncancerous lung sections from patients who had undergone surgery for lung cancer. We used immunohistochemistry to identify and quantify tryptase-positive mast cells and vimentin-positive fibroblasts. Fibrous tissue was identified by using EVG stain. Human mast cell line 1 (HMC-1) cells were co-cultured with pulmonary fibroblasts for 7 days using a transwell system, and IL-6, TGF-β, and VEGF expression in these cells was evaluated by RT-qPCR.

Results:

We found that the number of mast cells in labial salivary glands and lung tissues of patients with Sjögren syndrome was significantly increased compared to that in control subjects (p<0.001 and p<0.01, respectively). There was a significant negative correlation between the Saxon test results and the number of mast cells (r=0.81, P<0.01), suggesting the involvement of mast cells in decreased salivary secretion. The mast cells were usually present in close proximity to EVG-stained fibrous tissue in the labial salivary glands and lung tissues. Immunohistochemical analysis revealed that the mast cells were proximal to vimentin-positive fibroblasts. We hypothesized that mast cells were involved in the development of tissue fibrosis via modulation of fibroblast immune function, and conducted in vitro co-culture of HMC-1 cells and pulmonary fibroblasts. In these co-cultures, IL-6, TGF-ß, and VEGF expression was significantly increased compared to in mast cell or fibroblast monoculture. These observations suggest that an amplification loop is generated between mast cells and fibroblasts, enhancing production of IL-6, TGF-ß and VEGF.

Conclusion:

These results suggest a novel role for mast cells in the development of sialadenitis and interstitial lung disease in patients with Sjögren syndrome via induction of tissue fibrosis. An amplification loop between mast cells and fibroblasts enhances production of the pro-fibrotic factor, TGF-β, and angiogenic factor, VEGF, which may contribute to tissue fibrosis in sialadenitis and interstitial lung disease.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/mast-cells-are-involved-in-the-pathogenesis-of-sjogren-syndrome-by-inducing-tissue-fibrosis/