title: Toll-like receptor activation in basophils contributes to the development of IgG4-related disease.
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.
authors: Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Kyoto, Japan. tmhrwtnb@kuhp.kyoto-u.ac.jp
authors: Tomohiro
authors: T
authors: Watanabe
authors: Kouhei
authors: K
authors: Yamashita
authors: Toshiharu
authors: T
authors: Sakurai
authors: Masatoshi
authors: M
authors: Kudo
authors: Masahiro
authors: M
authors: Shiokawa
authors: Norimitsu
authors: N
authors: Uza
authors: Yuzo
authors: Y
authors: Kodama
authors: Kazushige
authors: K
authors: Uchida
authors: Kazuichi
authors: K
authors: Okazaki
authors: Tsutomu
authors: T
authors: Chiba
mesh_terms: D001327:Autoimmune Diseases / Q000276:immunology*; D053264:B-Cell Activating Factor / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology; D001491:Basophils / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology*; D018793:Interleukin-13 / Q000096:biosynthesis; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology*
chemical_list: D053264:B-Cell Activating Factor; D007074:Immunoglobulin G; D018793:Interleukin-13; D008024:Ligands; C505719:TNFSF13B protein, human; D051193:Toll-Like Receptors