T-bet upregulation and subsequent interleukin 12 stimulation are essential for induction of Th1 mediated immunopathology in Crohn's disease
K Matsuoka, N Inoue, T Sato, S Okamoto, T Hisamatsu… - Gut, 2004 - gut.bmj.com
Gut, 2004•gut.bmj.com
Background and aims: Many lines of evidence suggest that T helper cell type 1 (Th1)
immune responses predominate in Crohn's disease (CD). Recently, a novel transcription
factor T-box expressed in T cells (T-bet) has been reported as the master regulator of Th1
development. This study was designed to investigate the role of T-bet and proinflammatory
cytokines in Th1 mediated immunopathology in CD. Materials: CD4+ lamina propria
mononuclear cells (LPMCs) were isolated from surgically resected specimens (CD, n= 10; …
immune responses predominate in Crohn's disease (CD). Recently, a novel transcription
factor T-box expressed in T cells (T-bet) has been reported as the master regulator of Th1
development. This study was designed to investigate the role of T-bet and proinflammatory
cytokines in Th1 mediated immunopathology in CD. Materials: CD4+ lamina propria
mononuclear cells (LPMCs) were isolated from surgically resected specimens (CD, n= 10; …
Background and aims: Many lines of evidence suggest that T helper cell type 1 (Th1) immune responses predominate in Crohn’s disease (CD). Recently, a novel transcription factor T-box expressed in T cells (T-bet) has been reported as the master regulator of Th1 development. This study was designed to investigate the role of T-bet and proinflammatory cytokines in Th1 mediated immunopathology in CD.
Materials: CD4+ lamina propria mononuclear cells (LPMCs) were isolated from surgically resected specimens (CD, n = 10; ulcerative colitis (UC), n = 10; normal controls (NL), n = 5).
Methods: (1) T-bet expression of CD4+ LPMCs was examined by quantitative real time polymerase chain reaction and western blotting. (2) T-bet expression of LPMCs stimulated by interleukin (IL)-12/IL-18 was analysed by western blotting. (3) Interferon γ (IFN-γ) production and T-bet expression of CD4+ peripheral blood mononuclear cells (PBMCs) were examined with or without stimulation by anti-CD3/CD28 monoclonal antibodies and/or IL-12.
Results: (1) T-bet expression of CD4+ LPMCs was increased in CD compared with UC and NL. (2) Synergistically, augmentation of IFN-γ production by IL-12/IL-18 was independent of T-bet expression in LPMCs. (3) T-bet was induced by T cell receptor stimulation in CD4+ PBMCs. T-bet induction correlated with IFN-γ production and with augmentation of surface expressed IL-12 receptor β2.
Conclusions: T-bet induction by antigenic stimulation and subsequent stimulation by macrophage derived IL-12/IL-18 are important for establishing Th1 mediated immunopathology in CD.
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