Lymphotoxin targeted to salivary and lacrimal glands induces tertiary lymphoid organs and cervical lymphadenopathy and reduces tear production

Truman, Lucy; Bentley, Kevin L.; Ruddle, Nancy H.

doi:10.1002/eji.201948300

Cited by 3 publications

(1 citation statement)

References 32 publications

(42 reference statements)

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“…Lymphotoxin (LT) has been shown to be an important mediator in SS, both in patients and in animal models. [2][3][4][5][6] LTs are cytokines closely related to tumor necrosis factor (TNF). There are two forms of LTα: membrane bound and soluble.…”

Section: Introductionmentioning

confidence: 99%

Effect of lymphotoxin blockage on different stages of Sjogren's syndrome in an animal model

Shen

Nealon

et al. 2022

Rheumatology & Autoimmunity

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Background Lymphotoxin (LT) is an important mediator in Sjogren's syndrome (SS), both in patients and in animal models. Deletion of the LT alpha gene prevented the development of disease manifestations in the interelukin alpha transgenic mouse (IL14αTG) mouse model of SS. Aims The current study was designed to evaluate the use of LT inhibitors at different stages of the disease in IL14αTG mice. Materials and Methods IL14αTG mice were treated with anti‐LTa monoclonal antibody, LTb receptor‐immunoglobulin fusion protein (LTBR‐Ig) or isotype control during different stages of disease and analysis of salivary gland function, immunoglobulins, autoantibodies and histology of internal organs performed. Results and Discussion The inhibitors were very effective in maintaining salivary gland function and preventing infiltration of the glands with lymphocytes when used in the early stages of the disease. Blocking LT at later stages of the disease did not recover salivary gland function but was still effective in limiting extra glandular manifestations including eye disease and tumor development. Some differences were noted in the effectiveness of anti‐LTα versus LTBR‐Ig in limiting particular disease manifestations. Conclusion LT inhibitors deserve further investigation in the management of SS at whatever stage is identified.

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