Achaete-scute complex homologue 2 accelerates the development of Sjögren's syndrome-like disease in the NOD/ShiLtJ mouse

Immunol Lett. 2017 Oct:190:26-33. doi: 10.1016/j.imlet.2017.07.010. Epub 2017 Jul 17.

Abstract

Achaete-scute complex homologue 2 (Ascl2) has been reported to induce the differentiation and activation of follicular helper T (TFH) cells, which are essential for development of Sjögren's syndrome (SS). This study examined whether Ascl2 plays a role in the development of SS. NOD/ShiLtJ mice were injected with an Ascl2-overexpression vector, and the infiltration of lymphocytes into salivary and lacrimal glands was assessed. The expression of inflammatory cytokines and chemoattractants for T or B cells was measured. The activation of TFH cells was assessed using a specific marker of TFH cells. Ascl2 level was also measured in SS patients. Overexpression of Ascl2 increased the expression of C-X-C chemokine receptor type 5 (CXCR5) in both salivary and lacrimal glands (p<0.0001). Overexpression of Ascl2 also increased the expression of proinflammatory cytokines and chemoattractants including interleukin 6 (IL-6), tumor necrosis factor-α, IL-8, programmed cell death 1 (PD-1), IL-21, and B-cell lymphoma 6 (Bcl-6). Overexpression of Ascl2 increased the populations of CD4+CXCR5+, CD4+ICOS+, and CD4+PD-1+ cells. The Ascl2 level was higher in peripheral blood mononuclear cells from SS patients compared with those from healthy controls. Our findings suggest that Ascl2 may play a role in the development and progression of SS and may be a therapeutic target in the treatment of SS.

Keywords: Achaete-scute complex homologue 2; Follicular helper t cell; Sjögren’s syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cell Differentiation
  • Cells, Cultured
  • Cytokines / metabolism
  • Disease Models, Animal
  • Germinal Center / immunology
  • Humans
  • Lacrimal Apparatus / metabolism*
  • Mice
  • Mice, Inbred NOD
  • Proto-Oncogene Proteins c-bcl-6 / metabolism
  • Receptors, CXCR5 / metabolism
  • Salivary Glands / metabolism*
  • Sjogren's Syndrome / genetics*
  • T-Lymphocytes, Helper-Inducer / immunology*

Substances

  • ASCL2 protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • CXCR5 protein, human
  • Cytokines
  • Proto-Oncogene Proteins c-bcl-6
  • Receptors, CXCR5