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

To investigate the role of lymphotoxin (LT) in Sjögren's syndrome (SS) and in mucosal associated lymphoid tissue (MALT)‐lymphoma, we made transgenic mice (Amy1‐LTαβ) that targeted LTα and LTβ to the salivary and lacrimal glands. Amy1‐LTαβ mice developed atrophic salivary and lacrimal glands tha...

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Bibliographic Details
Published in:European journal of immunology 2020-03, Vol.50 (3), p.418-425
Main Authors: Truman, Lucy A., Bentley, Kevin L., Ruddle, Nancy H.
Format: Article
Language:English
Subjects:
Autoantibodies
Autoimmunity
Lacrimal gland and Nasolacrimal duct
Lymphadenopathy
Lymphoid tissue
Lymphoma
Lymphotoxin
MALT‐Lymphoma
Mucosa
Mucosal-associated lymphoid tissue
Sjogren's syndrome
Sjögren's syndrome
tertiary lymphoid organ
transgenic
Transgenic mice
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Summary:To investigate the role of lymphotoxin (LT) in Sjögren's syndrome (SS) and in mucosal associated lymphoid tissue (MALT)‐lymphoma, we made transgenic mice (Amy1‐LTαβ) that targeted LTα and LTβ to the salivary and lacrimal glands. Amy1‐LTαβ mice developed atrophic salivary and lacrimal glands that contained tertiary lymphoid organs (TLOs) and had reduced tear production. Amy1‐LTαβ mice developed cervical lymphadenopathy but not MALT‐lymphoma. TLO formation in the salivary and lacrimal glands of Amy1‐LTαβ was not sufficient to induce autoimmunity as measured by autoantibody titres. A mouse in which lymphotoxin is overexpressed in salivary and lacrimal glands exhibits some characteristics of Sjögren's syndrome, including lymphoid accumulations, termed tertiary lymphoid organs, at the sites of transgene expression, fewer tears, and enlarged draining LNs.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.201948300