T helper subsets in Sjögren's syndrome and IgG4-related dacryoadenitis and sialoadenitis: a critical review

J Autoimmun. 2014 Jun;51:81-8. doi: 10.1016/j.jaut.2013.07.007. Epub 2013 Aug 3.


IgG4-related disease (IgG4-RD) is a systemic disease characterized by the elevation of serum IgG4 and infiltration of IgG4-positive plasma cells in multiple target organs, including the pancreas, kidney, biliary tract and salivary glands. In contrast, Mikulicz's disease (MD) has been considered a subtype of Sjögren's syndrome (SS) based on histopathological similarities. However, it is now recognized that MD is an IgG4-RD distinguishable from SS and called as IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS). Regarding immunological aspects, it is generally accepted that CD4+ T helper (Th) cells play a crucial role in the pathogenesis of SS. Since it is well known that IgG4 is induced by Th2 cytokines such as interleukin (IL)-4 and IL-13, IgG4-DS is speculated to be a unique inflammatory disorder characterized by Th2 immune reactions. However, the involvement of Th cells in the pathogenesis of IgG4-DS remains to be clarified. Exploring the role of Th cell subsets in IgG4-DS is a highly promising field of investigation. In this review, we focus on the selective localization and respective functions of Th cell subsets and discuss the differences between SS and IgG4-DS to clarify the pathogenic mechanisms of these diseases.

Keywords: Cytokine; IgG4-related dacryoadenitis and sialoadenitis; IgG4-related disease; Sjögren's syndrome; T helper subset.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Dacryocystitis / immunology*
  • Dacryocystitis / metabolism
  • Humans
  • Immunoglobulin G / immunology*
  • Interleukins / metabolism
  • Sialadenitis / immunology*
  • Sialadenitis / metabolism
  • Sjogren's Syndrome / diagnosis
  • Sjogren's Syndrome / immunology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism


  • Cytokines
  • Immunoglobulin G
  • Interleukins
  • interleukin-21