Interleukin-4-triggered, STAT6-dependent production of a factor that induces mouse mast cell apoptosis.
IL-4 can suppress mast cell development from mouse spleen, bone marrow and peritoneal cells by an indirect process that is dependent on the presence of macrophages. Mast cells undergo apoptosis when exposed to supernatants collected from cultures of IL-4-stimulated peritoneal cells due to the IL-4-induced production of an apoptosis-inducing factor in the cultures. This effect of IL-4 is shown to be dependent on STAT6 signaling, because IL-4 and IL-13 do not suppress mast cell development from the spleen and peritoneal cells of STAT6-/- mice. Moreover, supernatants from cultures of IL-4- and IL-13-stimulated peritoneal cells of STAT6-/- mice do not exhibit apoptosis-inducing activity. We confirm, by using deficient mice, neutralizing antibodies and recombinant cytokines, that IL-4-induced apoptosis is not related to the well-known apoptosis-inducing factors Fas, Fas ligand, TNF-alpha, TRAIL, TGF-beta or perforin. These results demonstrate a novel mechanism whereby IL-4 and IL-13 can suppress mast cell development by inducing the production of an apoptosis-inducing factor from macrophages.
Hu
Zhi-Qing
ZQ
Department of Microbiology and Immunology, Showa University School of Medicine, Tokyo, Japan. zqhu@med.showa-u.ac.jp
Zhao
Wei-Hua
WH
Shimamura
Tadakatsu
T
Galli
Stephen J
SJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D008264:Macrophages / Q000502:physiology; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D050800:STAT6 Transcription Factor / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology; D018418:Th2 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000502:physiology
D018793:Interleukin-13; D050800:STAT6 Transcription Factor; D016212:Transforming Growth Factor beta; D015847:Interleukin-4