Toll-like receptor activation in basophils contributes to the development of IgG4-related disease

J Gastroenterol. 2013 Feb;48(2):247-53. doi: 10.1007/s00535-012-0626-8. Epub 2012 Jun 29.

Abstract

Background: IgG4-related disease (IRD) is characterized by systemic IgG4 antibody responses and by infiltration of IgG4-expressing plasma cells into the affected organs. Although T helper type 2 (Th2) cytokines are implicated in enhanced IgG4 responses, molecular mechanisms accounting for the development of IgG4 antibody responses are poorly defined. Since basophils function as antigen-presenting cells for Th2 responses, we tried to clarify the role of basophils in the development of IgG4 responses in this study.

Methods: IgG4 and cytokine responses to various nucleotide-binding oligomerization domain-like receptor and Toll-like receptor (TLR) ligands were examined by using basophils isolated from healthy controls and from patients with IgG4-related disease.

Results: Activation of TLRs in basophils from healthy controls induced IgG4 production by B cells, which effect was associated with enhanced production of B cell activating factor (BAFF) and IL-13. In addition, activation of TLRs in basophils from patients with IRD induced a large amount of IgG4 by B cells from healthy controls. This enhancement of IgG4 production was again associated with BAFF and IL-13.

Conclusions: These data suggest that innate immune responses mediated through TLRs may play a role in the development of IgG4-related disease, in part by production of BAFF from basophils.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoimmune Diseases / immunology*
  • B-Cell Activating Factor / biosynthesis
  • B-Lymphocytes / immunology
  • Basophils / immunology*
  • Humans
  • Immunity, Innate
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / immunology*
  • Interleukin-13 / biosynthesis
  • Ligands
  • Lymphocyte Activation / immunology
  • Signal Transduction / immunology
  • Toll-Like Receptors / immunology*

Substances

  • B-Cell Activating Factor
  • Immunoglobulin G
  • Interleukin-13
  • Ligands
  • TNFSF13B protein, human
  • Toll-Like Receptors