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

Eur J Immunol. 2020 Mar;50(3):418-425. doi: 10.1002/eji.201948300. Epub 2020 Feb 10.

Abstract

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.

Keywords: MALT-Lymphoma; Sjögren's syndrome; lymphotoxin; tertiary lymphoid organ; transgenic.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Lacrimal Apparatus / pathology*
  • Lymphadenopathy / genetics
  • Lymphadenopathy / pathology*
  • Lymphoma, B-Cell, Marginal Zone / genetics
  • Lymphoma, B-Cell, Marginal Zone / immunology
  • Lymphoma, B-Cell, Marginal Zone / pathology
  • Lymphotoxin-alpha / genetics
  • Lymphotoxin-alpha / metabolism*
  • Mice
  • Mice, Transgenic
  • Salivary Glands / pathology*
  • Sjogren's Syndrome / genetics
  • Sjogren's Syndrome / immunology
  • Sjogren's Syndrome / pathology
  • Tears / metabolism
  • Tertiary Lymphoid Structures / genetics
  • Tertiary Lymphoid Structures / pathology*

Substances

  • Lymphotoxin-alpha