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

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 develop...

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Bibliographic Details
Published in:Journal of gastroenterology 2013-02, Vol.48 (2), p.247-253
Main Authors: Watanabe, Tomohiro, Yamashita, Kouhei, Sakurai, Toshiharu, Kudo, Masatoshi, Shiokawa, Masahiro, Uza, Norimitsu, Kodama, Yuzo, Uchida, Kazushige, Okazaki, Kazuichi, Chiba, Tsutomu
Format: Article
Language:English
Subjects:
Abdominal Surgery
Autoimmune Diseases - immunology
B cells
B-Cell Activating Factor - biosynthesis
B-Lymphocytes - immunology
Basophils - immunology
Biliary Tract
Colorectal Surgery
Gastroenterology
Hepatology
Humans
Immunity
Immunity, Innate
Immunoglobulin G
Immunoglobulin G - biosynthesis
Immunoglobulin G - immunology
Interleukin-13 - biosynthesis
Ligands
Lymphocyte Activation - immunology
Medicine
Medicine & Public Health
Oligomers
Original Article—Liver
Pancreas
Signal Transduction - immunology
Surgical Oncology
Toll-Like Receptors - immunology
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Summary: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.
ISSN:0944-1174
1435-5922
DOI:10.1007/s00535-012-0626-8