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

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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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.

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Abbreviations

Ab:

Antibody

Ag:

Antigen

AIP:

Autoimmune pancreatitis

APC:

Antigen-presenting cell

BAFF:

B cell activating factor

ELISA:

Enzyme-linked immunosorbent assay

IRD:

IgG4-related disease

LPS:

Lipopolysaccharide

MDP:

Muramyl dipeptide

NOD2:

Nucleotide-binding oligomerization domain 2

NLR:

NOD-like receptor

PAM:

Pam3CSK4

PBMC:

Peripheral blood mononuclear cell

PGN:

Peptidoglycan

TLR:

Toll-like receptor

TSLP:

Thymic stromal lymphopoietin

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Acknowledgments

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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Authors and Affiliations

  1. Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Tomohiro Watanabe

  2. Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Tomohiro Watanabe, Masahiro Shiokawa, Norimitsu Uza, Yuzo Kodama & Tsutomu Chiba

  3. Department of Hematology and Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Kouhei Yamashita

  4. Department of Gastroenterology and Hepatology, Kinki University Graduate School of Medicine, Osakasayama, Japan

    Toshiharu Sakurai & Masatoshi Kudo

  5. Third Department of Internal Medicine, Kansai Medical University, Moriguchi, Japan

    Kazushige Uchida & Kazuichi Okazaki

Authors
  1. Tomohiro Watanabe
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  2. Kouhei Yamashita
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  3. Toshiharu Sakurai
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  4. Masatoshi Kudo
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  5. Masahiro Shiokawa
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  6. Norimitsu Uza
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  7. Yuzo Kodama
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  8. Kazushige Uchida
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  9. Kazuichi Okazaki
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  10. Tsutomu Chiba
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Correspondence to Tomohiro Watanabe.

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Watanabe, T., Yamashita, K., Sakurai, T. et al. Toll-like receptor activation in basophils contributes to the development of IgG4-related disease. J Gastroenterol 48, 247–253 (2013). https://doi.org/10.1007/s00535-012-0626-8

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  • DOI: https://doi.org/10.1007/s00535-012-0626-8

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