Novel role of interleukin 7 in myelopoiesis: stimulation of primitive murine hematopoietic progenitor cells.

Jacobsen, Frede W.; Veiby, O. Petter; Skjønsberg, Cecilia; Jacobsen, Sten Eirik W.

doi:10.1084/jem.178.5.1777

Cited by 35 publications

(10 citation statements)

References 33 publications

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“…Stimulation of T lymphopoiesis at the expense of myeloid development by coproduction of HuIL‐7 and IL‐3 in the mice was unexpected. Although IL‐7 is known to be important in early lymphopoiesis [17, 18], it has been reported to also have stimulatory effects on human myelopoiesis in vitro [19]. Thus, our results might be attributed to the interaction of IL‐3 and IL‐7 together with cross‐reactive cytokines from the murine microenvironment.…”

Section: Resultsmentioning

confidence: 79%

Long‐Term Cytokine Production from Engineered Primary Human Stromal Cells Influences Human Hematopoiesis in an In Vivo Xenograft Model

1997

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Human hematopoiesis can be supported in beige/nude/ XID (bnx) mice by coinjection of human bone marrow stromal cells engineered to secrete human interleukin 3 (HuIL-3). The major limitation is a total absence of human B cell development in the mice, which could be due to supraphysiological levels of HuIL-3 in the circulation. In an effort to obtain human B lymphoid, as well as T lymphoid and myeloid cell development in the mice, CD34 + cells were coinjected with human marrow stromal cells engineered to secrete human IL-2, IL-7, stem cell factor or FLT3 ligand, ± IL-3. No single factor other than IL-3 supported sustained human hematopoiesis in the mice, although cytokines were expressed for four to six months post-transplantation. Production of both HuIL-3 and IL-7 in the mice supported extrathymic development of human T lymphocytes, but no B cells, myeloid cells, or clonogenic progenitors were detected. Human B cells were not produced from CD34 + cells in the bnx mice under any condition tested. Another limitation to the bnx/Hu system is a lack of maturation of human red blood cells, although BFU-E are maintained. Stromal cells secreting human erythropoietin and IL-3 were cotransplanted into mice with HuCD34 + cells and an increase in hematocrit from 40%-45% to 80%-85% resulted, with production of human and murine red blood cells. Unfortunately, all mice (n = 9) suffered strokes, displayed paralysis and died within three weeks. The bnx/Hu cotransplantation model provides an interesting system in which to study human hematopoietic cell differentiation under the influence of various cytokines.

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Section: Resultsmentioning

confidence: 79%

Long‐Term Cytokine Production from Engineered Primary Human Stromal Cells Influences Human Hematopoiesis in an In Vivo Xenograft Model

1997

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“…Although myeloid‐lineage cells, including the common myeloid progenitor (CMP), do not express IL‐7R (Akashi et al ., 2000), several experiments have shown that IL‐7 can result in various effects on myeloid lineage cells both in vitro and in vivo . IL‐7 synergistically increases myeloid colony formation of Lin − Sca‐1 + progenitors when combined with various colony‐stimulating factors, including GM‐CSF and CSF‐1 (Jacobsen et al ., 1993; Appasamy, 1999). In addition, administration of recombinant IL‐7 to mice has been shown to increase the numbers of immature myeloid lineage cells, which further supports a direct or indirect function of IL‐7 in myelopoiesis (Faltynek et al ., 1992).…”

Section: Introductionmentioning

confidence: 99%

Determination of lymphoid cell fate is dependent on the expression status of the IL-7 receptor

et al. 2003

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Signaling through the IL-7 receptor (IL-7R) is necessary for the development of the earliest B-and T-lineage cells. IL-7R is ®rst expressed on common lymphoid progenitor cells and is not detected on primitive common myeloid progenitors. In this study, we show that enforced expression of IL-7R on multipotential stem cells does not in¯uence lymphoid versus myeloid cell fate. T cell development was compatible with sustained IL-7R expression; however, we observed a near complete block in B cell development at the onset of B-lineage commitment. Unlike preproB cells from control animals, developmentallyarrested IL-7R + B220 + CD19 ± NK1.1 ± Ly-6C ± cells failed to express EBF and Pax5. These results suggest that transient downregulation of IL-7R signaling is a necessary event for induction of EBF and Pax5 expression and B-lymphocyte commitment.

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“…However, there are a few reports which suggest that exogenously administered IL-7 can elicit other hemopoietic effects. In vitro, in combination with a number of CSF, IL-7 was shown to increase the number of colonies formed by primitive murine hemopoietic progenitors (Lin Ϫ Sca ϩ ), but it was ineffective when used alone, and it did not affect myeloid differentiation induced by the CSF (14). IL-7R is expressed on Lin Ϫ ScaI low lymphoid progenitors, which did not show myeloid differentiation potential (15).…”

Section: Il-7 Induces Myelopoiesis and Erythropoiesismentioning

confidence: 99%

IL-7 Induces Myelopoiesis and Erythropoiesis

Aiello

Keller

Klarmann

et al. 2007

The Journal of Immunology

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IL-7 administration to mice was previously reported to increase the mobilization of progenitor cells from marrow to peripheral sites. We now report that IL-7 increases the number of mature myeloid and monocytic cells in spleen and peripheral blood. This effect required T cells, and we show that IL-7 treatment in vivo induced GM-CSF and IL-3 production by T cells with memory phenotype. However, additional myelopoietic cytokines were shown to be involved because mice deficient in both GM-CSF and IL-3 also responded to IL-7 with increased myelopoiesis. Candidate cytokines included IFN-γ and Flt3 ligand, which were also produced in response to IL-7. Because IFN-γ-deficient mice also increased myelopoiesis, it was suggested that IL-7 induced production of redundant myelopoietic cytokines. In support of this hypothesis, we found that the supernatant from IL-7-treated, purified T cells contained myelopoietic activity that required a combination of Abs against GM-CSF, IL-3, and anti-Flt3 ligand to achieve maximum neutralization. IL-7 administration increased the number of splenic erythroid cells in either normal, Rag1 or GM-CSF-IL-3-deficient mice, suggesting that IL-7 might directly act on erythroid progenitors. In support of this theory, we detected a percentage of TER-119+ erythroid cells that expressed the IL-7Rα-chain and common γ-chain. Bone marrow cells expressing IL-7R and B220 generated erythroid colonies in vitro in response to IL-7, erythropoietin, and stem cell factor. This study demonstrates that IL-7 can promote nonlymphoid hemopoiesis and production of cytokines active in the host defense system in vivo, supporting its possible clinical utility.

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Novel role of interleukin 7 in myelopoiesis: stimulation of primitive murine hematopoietic progenitor cells.

Cited by 35 publications

References 33 publications

Long‐Term Cytokine Production from Engineered Primary Human Stromal Cells Influences Human Hematopoiesis in an In Vivo Xenograft Model

Long‐Term Cytokine Production from Engineered Primary Human Stromal Cells Influences Human Hematopoiesis in an In Vivo Xenograft Model

Determination of lymphoid cell fate is dependent on the expression status of the IL-7 receptor

IL-7 Induces Myelopoiesis and Erythropoiesis

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