Published in:
01-02-2013 | Original Article—Liver, Pancreas, and Biliary Tract
Toll-like receptor activation in basophils contributes to the development of IgG4-related disease
Authors:
Tomohiro Watanabe, Kouhei Yamashita, Toshiharu Sakurai, Masatoshi Kudo, Masahiro Shiokawa, Norimitsu Uza, Yuzo Kodama, Kazushige Uchida, Kazuichi Okazaki, Tsutomu Chiba
Published in:
Journal of Gastroenterology
|
Issue 2/2013
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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.