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.
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: Y Masaki; L Dong; N Kurose; K Kitagawa; Y Morikawa; M Yamamoto; H Takahashi; Y Shinomura; K Imai; T Saeki; A Azumi; S Nakada; E Sugiyama; S Matsui; T Origuchi; S Nishiyama; I Nishimori; T Nojima; K Yamada; M Kawano; Y Zen; M Kaneko; K Miyazaki; K Tsubota; K Eguchi; K Tomoda; T Sawaki; T Kawanami; M Tanaka; T Fukushima; S Sugai; H Umehara Journal: Ann Rheum Dis Date: 2008-08-13 Impact factor: 19.103
Authors: Karthik Ravi; Suresh T Chari; Santhi S Vege; William J Sandborn; Thomas C Smyrk; Edward V Loftus Journal: Inflamm Bowel Dis Date: 2009-09 Impact factor: 5.325
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