IL-17 and CCR9+α4β7- Th17 Cells Promote Salivary Gland Inflammation, Dysfunction, and Cell Death in Sjögren's Syndrome

Front Immunol. 2021 Sep 1;12:721453. doi: 10.3389/fimmu.2021.721453. eCollection 2021.


Previous studies have evaluated the roles of T and B cells in the pathogenesis of Sjögren's syndrome (SS); however, their relationships with age-dependent and metabolic abnormalities remain unclear. We examined the impacts of changes associated with aging or metabolic abnormalities on populations of T and B cells and SS disease severity. We detected increased populations of IL-17-producing T and B cells, which regulate inflammation, in the salivary glands of NOD/ShiLtJ mice. Inflammation-induced human submandibular gland cell death, determined based on p-MLKL and RIPK3 expression levels, was significantly increased by IL-17 treatment. Among IL-17-expressing cells in the salivary gland, peripheral blood, and spleen, the α4β7 (gut-homing integrin)-negative population was significantly increased in aged NOD/ShiLtJ mice. The α4β7-positive population markedly increased in the intestines of aged NOD/ShiLtJ mice following retinoic acid (RA) treatment. A significant increase in α4β7-negative IL-17-expressing cells in salivary glands may be involved in the onset and progression of SS. These results suggest the potential therapeutic utility of RA in SS treatment.

Keywords: Sjögren’s syndrome; aging; gut-homing; interleukin 17; retinoic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Blood Glucose
  • Cell Death
  • Cell Self Renewal
  • Disease Models, Animal
  • Disease Susceptibility
  • Interleukin-17 / blood
  • Interleukin-17 / metabolism*
  • Mice
  • Receptors, CCR / metabolism*
  • Receptors, Lymphocyte Homing / metabolism*
  • Salivary Glands / immunology
  • Salivary Glands / metabolism
  • Salivary Glands / pathology
  • Sjogren's Syndrome / etiology*
  • Sjogren's Syndrome / metabolism*
  • Sjogren's Syndrome / pathology
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Th17 Cells / immunology*
  • Th17 Cells / metabolism*


  • Biomarkers
  • Blood Glucose
  • CC chemokine receptor 9
  • IL17A protein, human
  • Interleukin-17
  • Receptors, CCR
  • Receptors, Lymphocyte Homing