IL-4 induces differentiation and expansion of Th2 cytokine-producing eosinophils.
Innate effector cells that produce Th2-type cytokines are critical in Th2 cell-mediated immune responses. However, it is not known how these cells acquire the ability to produce Th2 cytokines. IL-4 is a potent inducer that directs differentiation of naive CD4(+) T cells into CD4(+) Th2 effector cells. To determine whether IL-4 can induce differentiation and expansion of Th2 cytokine-producing innate cells, we used mice whose il-4 gene was replaced by a knock-in green fluorescence protein (gfp) gene. We found that, directly ex vivo, IL-4 increased the number of GFP(+) cells in the airway and the lung tissue in an Ag-specific manner. The majority of GFP(+) cells were eosinophils, suggesting that IL-4 plays a pivotal role in expanding IL-4-producing eosinophils in vivo. IL-4-producing eosinophils showed some unique features compared with IL-4-producing CD4(+) T cells. They exhibited biallelic expression of the il-4 gene when stimulated and were more dominant IL-4- and IL-5-producing cells. Furthermore, we show that IL-4 drove bone marrow progenitor cells to differentiate into Th2 cytokine-producing eosinophils in vitro. These results strongly suggest IL-4 is a potent factor in directing bone marrow progenitor cells to differentiate into Th2 cytokine-producing eosinophils.
Chen
Luqiu
L
Department of Cell Biology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA.
Grabowski
Kristy A
KA
Xin
Jun-Ping
JP
Coleman
John
J
Huang
Zan
Z
Espiritu
Baltazar
B
Alkan
Serhan
S
Xie
H Bill
HB
Zhu
Yuechun
Y
White
Fletcher A
FA
Clancy
John
J
Huang
Hua
H
D000483:Alleles; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D001980:Bronchi / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D006580:Genetic Carrier Screening; D049452:Green Fluorescent Proteins; D006720:Homozygote; D015847:Interleukin-4 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015848:Interleukin-5 / Q000096:biosynthesis; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000473:pathology; D013234:Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D015848:Interleukin-5; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D015847:Interleukin-4