title: Overexpression of interleukin 21 induces expansion of hematopoietic progenitor cells.
abstract: The interleukin 21 (IL-21) receptor is expressed on T-cells, B-cells, and natural killer cells, and IL-21 is critical for regulating immunoglobulin production in vivo in cooperation with IL-4. So far, however, little is known about a role for IL-21 outside the immune system. We investigated the effect of IL-21 on hematopoiesis in vivo by using the hydrodynamics gene-delivery method. Overexpression of IL-21 increases Sca-1+ cells in the periphery and spleen. It also increases the numbers of c-Kit+, Sca-1+, and lineage-/low (KSL) cells and colony-forming units-granulocyte-macrophage (CFU-GM) in the spleen, indicating the expansion of hematopoietic progenitor cells. We found that even in RAG2-/- mice, which lack mature T-cells and B-cells, IL-21 induced an increase in KSL cells and CFU-GM in the spleen. These results demonstrate that IL-21 can induce the expansion of hematopoietic progenitor cells in vivo, even in the absence of mature T-cells and B-cells.
authors.affiliation: Division of Hematopoietic Factors, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ozakikat@jichi.ac.jp
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Ozaki
authors.forename: Ai
authors.initials: A
authors.lastname: Hishiya
authors.forename: Keiko
authors.initials: K
authors.lastname: Hatanaka
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakajima
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Patrick
authors.initials: P
authors.lastname: Hwu
authors.forename: Toshio
authors.initials: T
authors.lastname: Kitamura
authors.forename: Keiya
authors.initials: K
authors.lastname: Ozawa
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Leonard
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nosaka
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D000950:Antigens, Ly / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism; D015870:Gene Expression; D042381:Granulocyte Precursor Cells / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D007378:Interleukins / Q000096:biosynthesis*; D008214:Lymphocytes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D053655:Receptors, Interleukin-21 / Q000096:biosynthesis; D000098546:Interleukin-21
chemical_list: D000950:Antigens, Ly; D004268:DNA-Binding Proteins; D007378:Interleukins; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; C499308:Rag2 protein, mouse; D053655:Receptors, Interleukin-21; D015847:Interleukin-4; D000098546:Interleukin-21