Toll-like receptor activation in basophils contributes to the development of IgG4-related disease
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.
KeywordsIgG4-related disease Basophil TLR
B cell activating factor
Enzyme-linked immunosorbent assay
Nucleotide-binding oligomerization domain 2
Peripheral blood mononuclear cell
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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