Negative control of basophil expansion by IRF-2 critical for the regulation of Th1/Th2 balance.
Although basophils are known to produce interleukin 4 (IL-4), the roles of these cells have been documented only in mice infected with parasites or in the effector phase of allergic inflammations. Here we show that naive mice lacking the transcription factor, interferon regulatory factor 2 (IRF-2), exhibited signal transducer and activator of transcription 6 (Stat6)-independent expansion of basophils in the periphery. IRF-2 appeared to act autonomously in the cells to negatively regulate the expansion of, but not cytokine production by, basophils. Spontaneous Th2 polarization of CD4+ T cells was observed in these mice and the genetic reduction of basophil numbers by mutating the Kit gene abolished such a polarization in vivo. We also found that both basophils and IL-4 derived from them were indeed essential for Th2 development under neutral conditions in vitro. Furthermore, neutralization of IL-3 abolished IL-4 production by basophils during Th1/Th2 differentiation cultures and subsequent Th2 development. These results indicated that basophils acted as a cellular converter to turn the neutral IL-3 into the Th2-inducing IL-4 during the initiation of Th1/Th2 differentiation. Thus, the negative regulatory role of IRF-2 on the basophil population size is critically important for preventing excess Th2 polarization and the Th1/Th2 balance in naive animals.
Hida
Shigeaki
S
Department of Immunology and Infectious Diseases, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
Tadachi
Masumi
M
Saito
Takashi
T
Taki
Shinsuke
S
D000818:Animals; D001491:Basophils / Q000166:cytology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000502:physiology*; D006706:Homeostasis; D050836:Interferon Regulatory Factor-2; D007377:Interleukin-3 / Q000502:physiology; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D012097:Repressor Proteins / Q000502:physiology*; D018417:Th1 Cells / Q000166:cytology*; D018418:Th2 Cells / Q000166:cytology*; D014157:Transcription Factors / Q000172:deficiency / Q000502:physiology*
D016207:Cytokines; D004268:DNA-Binding Proteins; D050836:Interferon Regulatory Factor-2; D007377:Interleukin-3; C494230:Irf2 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; D015847:Interleukin-4