The Role of Lymphotoxin Receptor Signaling in Diseases

Tumanov, Alexei V.; Christiansen, Peter A.; Fu, Yang–Xin

doi:10.2174/156652407781695701

Cited by 26 publications

(24 citation statements)

References 133 publications

(217 reference statements)

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“…Due to its direct cytotoxic effects, LTA has been directly implicated in the pathogenesis of human polymyositis (22). In animal models, blocking LTA action inhibited both induced and spontaneous forms of autoimmune diseases including collagen-induced arthritis, inflammatory bowel disease, myasthenia gravis, insulin-dependent diabetes, and multiple sclerosis (23,24). In this paper, we demonstrate that in the IL14aTG animal model, LTA is a critical factor in the pathogenesis of Sjögren's disease.…”

mentioning

confidence: 65%

“…LTA has been implicated as having diverse effects on the pathogenesis of autoimmune disorders. One potential role for membranebound LTA would be to increase the production of ectopic lymphoid tissues in particular organs leading to the development of more efficient local autoreactive responses (24,42). A soluble LTBR-Ig was produced to investigate this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

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A Role for Lymphotoxin in Primary Sjögren’s Disease

Shen

Suresh

et al. 2010

The Journal of Immunology

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The etiology of salivary gland injury in primary Sjögren’s disease is not well understood. We have previously described a mouse model of Sjögren’s disease, IL-14α transgenic (IL14αTG) mice, which reproduces many of the features of the human disease. We now demonstrate a critical role for lymphotoxin α (LTA) in the pathogenesis of Sjögren’s disease in IL14αTG mice. IL14αTG mice express LTA mRNA in their salivary glands and spleen and produce soluble LTA protein in their salivary secretions. When IL14αTG mice were crossed with LTA−/− mice, the IL14αTG.LTA−/− mice retained normal salivary gland secretions and did not develop either lymphocytic infiltration of their salivary glands or secondary lymphomas. However, both IL14αTG and IL14αTG.LTA−/− mice produced similar amounts of IFN-α and had similar deposition of autoantibodies in their salivary glands. Both IL14α and IL14α/LTA−/− mice had similar B cell responses to T-dependent and T-independent Ags, L-selectin expression, and expression of RelA, RelB, and NF-κB2 in their spleens. These studies suggest that LTA plays a critical role in the local rather than systemic inflammatory process of Sjögren’s disease. Furthermore, local production of soluble LTA in the salivary glands of IL14αTG mice is necessary for the development of overt Sjögren’s disease. Autoantibody deposition alone is not sufficient to produce salivary gland dysfunction. We also demonstrate that LTA is increased in the salivary gland secretions and sera of patients with Sjögren’s disease, further strengthening the biological relevance of the IL14αTG model to understanding the pathogenesis of human disease.

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confidence: 65%

Section: Discussionmentioning

confidence: 99%

A Role for Lymphotoxin in Primary Sjögren’s Disease

Shen

Suresh

et al. 2010

The Journal of Immunology

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“…One of the major quantitative trait loci (QTL) sites identified for pulmonary carcinogenesis models is on chromosome 17, as well as most pulmonary inflammation models [25], and TNF resides within this QTL. Interestingly, TNF is clustered with the two lymphotoxin (LT; Ltα and LTβ) genes, which can also bind to TNF receptors, in addition to the LT receptor [154][155][156], all of which are important in the inflammation models, such as ozone exposure. Thus, the involvement of the TNF cluster in pulmonary carcinogenesis is likely.…”

Section: Nuclear Factor Kappa B (Nfκb)mentioning

confidence: 99%

Inflammation and Lung Cancer: Prevention

Bauer

Miller

Keith

2015

Inflammation and Lung Cancer

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In this chapter, the authors focus on preclinical animal modeling including the basic science connecting inflammation and lung cancer chemoprevention, preclinical testing in animal models, clinical trials, and future directions. Animal models consistently demonstrate that certain inflammatory pathways are clearly important in lung carcinogenesis. Many of these pathways, such as NRF2, PPARγ, and NFκB, are linked to multiple cancer stages (i.e., initiation, promotion, progression, and metastasis) and some (e.g., NRF2, PPARγ) are linked to both pro-and anti-inflammatory pathways depending on the stage. This emphasizes the importance of a stage-dependent approach to therapy. In addition, these early animal studies often identify systemic problems (e.g., cardiac effects of COX-2-specific inhibitors). Although no Phase III trials with lung cancer as the primary endpoint have generated the robust data that would be needed to make recommendations for chemoprevention, both low-dose aspirin and inhaled corticosteroids are of interest for further study. Iloprost has significant preclinical and Phase II data to support further investigation.

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“…Pleiotropic functions are attributed to LT -in health and disease [90] -which in some instances can go beyond the well-documented role of LT in the development and maintenance of lymphoid organs. This includes, e.g., an important role of LT signaling in the acceptance of donor stem cells, controlling cuprizone-induced demyelination, the progress of experimental autoimmune encephalomyelitis (EAE), the control of lipid metabolism or liver regeneration [34,58,67,80,91].…”

Section: Ltβr Signaling In Health and Diseasementioning

confidence: 99%