IL-18 induction of IgE: dependence on CD4+ T cells, IL-4 and STAT6.
Overproduction of immunoglobulin E (IgE) and T helper cell type 2 (TH2) cytokines, including interleukin 4 (IL-4), IL-5 and IL-13, can result in allergic disorders. Although it is known that IL-4 is critical to the polarization of naïve CD4+ T cells to a TH2 phenotype, both in vitro and in many in vivo systems, other factors that regulate in vivo IL-4 production and TH2 commitment are poorly understood. IL-18, an IL-1-like cytokine that requires cleavage with caspase-1 to become active, was found to increase IgE production in a CD4+ T cells-, IL-4- and STAT6-dependent fashion. IL-18 and T cell receptor-mediated stimulation could induce naïve CD4+ T cells to develop into IL-4-producing cells in vitro. Thus, caspase-1 and IL-18 may be critical in regulation of IgE production in vivo, providing a potential therapeutic target for allergic disorders.
Yoshimoto
T
T
Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Hyogo, 663-8501, Japan.
Mizutani
H
H
Tsutsui
H
H
Noben-Trauth
N
N
Yamanaka
K
K
Tanaka
M
M
Izumi
S
S
Okamura
H
H
Paul
W E
WE
Nakanishi
K
K
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand / Q000235:genetics; D020170:Caspase 1 / Q000235:genetics / Q000276:immunology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology*; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D015440:Leprosy, Lepromatous / Q000097:blood / Q000276:immunology; D015441:Leprosy, Tuberculoid / Q000097:blood / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000276:immunology; D050800:STAT6 Transcription Factor; D018418:Th2 Cells / Q000276:immunology / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology*
D020382:Interleukin-18; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D023201:CD40 Ligand; D015847:Interleukin-4; D007073:Immunoglobulin E; D020170:Caspase 1