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Craniofacial Development, Oral Infections and Inflammations

The Lymphotoxin-beta receptor (LTBR) signaling pathway studied in Sjögren´s syndrome like disease in NOD mice

Sjögren´s syndrome is characterized by dry eyes and dry mouth caused by reduced tear- and saliva secretion. The disease pathogenesis is still not clear, and the treatment is only symptomatic. Also, specific diagnostic tests are not available. The aim of these studies was to determine the effects of LTBR pathway blockade on Sjögren´s syndrome like salivary gland disease in NOD mice.

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Sjögren´s syndrome is characterized by dry eyes and dry mouth caused by reduced tear- and saliva secretion. The disease pathogenesis is still not clear, and the treatment is only symptomatic. Also, specific diagnostic tests are not available. The aim of these studies was to determine the effects of LTBR pathway blockade on Sjögren´s syndrome like salivary gland disease in NOD mice.


The LTBR signaling pathway plays a key role in development and maintenance of secondary lymphoid structures. Secondary lymphoid structures are found in salivary glands of patients with Sjögren´s syndrome. In a microarray study, we found LTB to be one of the genes that were highest expressed in salivary glands of Sjögren syndrome patients compared to healthy individuals. These results were therefore followed up with further functional studies in mice.


In the present project it was investigated if blocking of the LTBR signaling pathway with a LTBR antagonist, the LTBR-Ig fusion protein, could inhibit development or reduce the size of the inflammatory infiltrate in salivary glands in a mouse model with Sjögren´s syndrome like disease.


The treatment demonstrated that B- and T-cell zones were reduced in number and size in the salivary glands. Lymphoid neogenesis was also inhibited by the treatment, and saliva flow was improved. The cytokine profile of the mice resembled more those of mice in prediseased state.


There are more studies ongoing on this subject.


People:

Professor Anne Isine Bolstad (Principal investigator), Department of Clinical Dentistry -

Periodontics

Professor Kathrine Skarstein. The Gade Institute - Section of Pathology.

 

There are also international collaborators in this project.

The project is supported by Helse Vest.


https://www.uib.no/personer/Anne.Bolstad

https://www.uib.no/personer/Kathrine.Skarstein

 

Publications:

Blockade of lymphotoxin-beta receptor signaling reduces aspects of Sjögren syndrome in salivary glands of non-obese diabetic mice. Gatumu MK, Skarstein K, Papandile A, Browning JL, Fava RA, Bolstad AI. Arthritis Res Ther. 2009 Feb 18;11(1):R24.