Fingolimod reduces salivary infiltrates and increases salivary secretion in a murine Sjögren's model

J Autoimmun. 2020 Dec:115:102549. doi: 10.1016/j.jaut.2020.102549. Epub 2020 Oct 13.

Abstract

Sjögren's Syndrome (SjS) is a chronic, systemic autoimmune disease causing xerostomia, xerophthalmia, and systemic symptoms. The principal pathological finding in SjS is the accumulation of lymphocytes in exocrine glandular tissue and elsewhere, leading to secretory dysfunction and other abnormalities. A rational therapeutic approach might be to interfere with lymphocyte migration to the periphery from central lymphoid tissues. We thus examined in an animal model of SjS the effects of Fingolimod (FTY720, Gilenya™), which interferes with migration of lymphocytes to peripheral sites. Fingolimod induces sequestration of lymphocytes in lymphoid organs by altering lymphocyte expression of sphingosine-1-phosphate receptors. In the C57Bl/6. NOD.Aec1Aec2 (AEC) model of SjS, Fingolimod reduced circulating T and B cell numbers. Treatment of AEC mice with Fingolimod increased salivary output and decreased the size of salivary gland infiltrates. Oral Fingolimod thus merits further consideration in the management of SjS in humans.

Keywords: Autoimmunity; Fingolimod; Lymphocyte trafficking; Sjogren's syndrome; Sphingosine receptors.

Publication types

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

MeSH terms

  • Administration, Oral
  • Animals
  • Disease Models, Animal
  • Female
  • Fingolimod Hydrochloride / administration & dosage*
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Saliva / metabolism*
  • Salivary Glands / drug effects*
  • Salivary Glands / immunology
  • Salivary Glands / metabolism
  • Salivary Glands / pathology
  • Sjogren's Syndrome / drug therapy*
  • Sjogren's Syndrome / genetics
  • Sjogren's Syndrome / immunology
  • Sjogren's Syndrome / pathology

Substances

  • Fingolimod Hydrochloride