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Abstract Number: 2807

Activation of the STING Pathway Is a Shared Feature of Salivary Gland and Lung Inflammation in Sjogren’s Syndrome

Joanna Papinska 1, Grzegorz Gmyrek 2, Umesh Deshmukh1 and Harini Bagavant 1, 1Oklahoma Medical Research Foundation, Oklahoma City, OK, 2Oklahoma Medical Research Foundation, Oklahoma City

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: innate immunity, lung and ILC, Salivary gland, Sjogren's syndrome

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Session Information

Date: Tuesday, November 12, 2019

Session Title: 5T110: Innate Immunity (2804–2809)

Session Type: ACR Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: Sjögren’s syndrome is a chronic autoimmune disorder characterized by an increased type 1 interferon gene signature. The engagement of stimulator of interferon genes (STING) is a critical pathway involved in the production of type I IFNs. The gain of function mutations in TMEM173, encoding STING, results in a severe vasculopathy affecting the skin and lungs. We have previously reported that systemic activation of the STING pathway in mice, using a STING agonist DMXAA, causes an Sjögren’s syndrome-like disease characterized by sialoadenitis and salivary gland dysfunction. Considering that lungs are affected in 9-20% of Sjögren’s syndrome patients, this study was undertaken to investigate lung involvement in DMXAA treated mice.

Methods: Female C57BL/6 mice (8-10 wks. old) were injected with DMXAA ((20mg/kg body wt) either once (day 0) or twice (days 0 and 21). Serum IFN-α and IFN-β levels  were measured by a multiplex bead-based assay. Proinflammatory cytokine gene expression in lungs was analyzed by real-time PCR and by using the Nanostring mouse inflammation panel. The innate lymphoid cell populations and lymphatic endothelial cells in lungs were studied by flow cytometry. H&E stained lung sections were used to evaluate the presence of inflammatory foci in the lungs. The role of STING expression in hematopoietic cells on lung inflammation, was investigated in bone marrow chimeras of WT into STING-/- mice and vice versa.

Results: DMXAA treatment induced a rapid, but transient spike in circulating type I IFN levels, which returned to baseline in 24h. At 4h post-treatment, there was a significant increase in the expression of IL-6, TNF-α, IFNβ, Mx1, and IFNγ, in the lungs. This was followed by an increase in type 1 innate lymphoid cells on day 8.  Histopathologic analysis showed the presence of peri-bronchial inflammatory infiltrates on day 35, which persisted until day 57. The lung inflammation was associated with an increased expression of multiple proinflammatory genes, including Ccl20, Cxcl10, Cxcl9, and Il17α. Also, there was an increased frequency of lymphatic endothelial cells, suggestive of lymphangiogenesis. Although STING expression was seen in bronchial epithelium and alveolar cells, bone marrow chimeras between STING-/- and wild type mice suggest that STING expression in bone marrow derived cells was critical for lung inflammation.

Conclusion: Our data suggest that systemic activation of STING is a common pathway involved in the induction of salivary gland and lung inflammation in Sjögren’s syndrome. In addition, activation of innate immunity in bone marrow-derived cells is critical for initiating lymphocytic infiltration in organs targeted in Sjögren’s syndrome.


Disclosure: J. Papinska, None; G. Gmyrek, None; U. Deshmukh, None; H. Bagavant, None.

To cite this abstract in AMA style:

Papinska J, Gmyrek G, Deshmukh U, Bagavant H. Activation of the STING Pathway Is a Shared Feature of Salivary Gland and Lung Inflammation in Sjogren’s Syndrome [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/activation-of-the-sting-pathway-is-a-shared-feature-of-salivary-gland-and-lung-inflammation-in-sjogrens-syndrome/. Accessed April 17, 2021.
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