Journal of Gastroenterology

, Volume 48, Issue 2, pp 247–253 | Cite as

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

  • Tomohiro WatanabeEmail author
  • Kouhei Yamashita
  • Toshiharu Sakurai
  • Masatoshi Kudo
  • Masahiro Shiokawa
  • Norimitsu Uza
  • Yuzo Kodama
  • Kazushige Uchida
  • Kazuichi Okazaki
  • Tsutomu Chiba
Original Article—Liver, Pancreas, and Biliary Tract



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.


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.


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.


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.


IgG4-related disease Basophil TLR 







Autoimmune pancreatitis


Antigen-presenting cell


B cell activating factor


Enzyme-linked immunosorbent assay


IgG4-related disease




Muramyl dipeptide


Nucleotide-binding oligomerization domain 2


NOD-like receptor




Peripheral blood mononuclear cell




Toll-like receptor


Thymic stromal lymphopoietin



This work is supported in part by grants from the Ministry of Education, Science and Culture, Japan, and the Japan Society for the Promotion of Science (21590532); Takeda Science Foundation; Astellas Foundation for Research on Metabolic Disorders; Yakult Bioscience Foundation; Cell Science Research Foundation; Kato Memorial Trust for Nambyo Research; Pancreas Research Foundation of Japan; Uehara Memorial Foundation (to T. W.); and Health and Labour Sciences Research Grants for research on intractable diseases from the Ministry of Health, Labour and Welfare of Japan (to T. C.).

Conflict of interest

The authors have declared no conflicts of interest.


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Copyright information

© Springer 2012

Authors and Affiliations

  • Tomohiro Watanabe
    • 1
    • 2
    Email author
  • Kouhei Yamashita
    • 3
  • Toshiharu Sakurai
    • 4
  • Masatoshi Kudo
    • 4
  • Masahiro Shiokawa
    • 2
  • Norimitsu Uza
    • 2
  • Yuzo Kodama
    • 2
  • Kazushige Uchida
    • 5
  • Kazuichi Okazaki
    • 5
  • Tsutomu Chiba
    • 2
  1. 1.Center for Innovation in Immunoregulative Technology and TherapeuticsKyoto University Graduate School of MedicineKyotoJapan
  2. 2.Department of Gastroenterology and HepatologyKyoto University Graduate School of MedicineKyotoJapan
  3. 3.Department of Hematology and OncologyKyoto University Graduate School of MedicineKyotoJapan
  4. 4.Department of Gastroenterology and HepatologyKinki University Graduate School of MedicineOsakasayamaJapan
  5. 5.Third Department of Internal MedicineKansai Medical UniversityMoriguchiJapan

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