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Article: AAV-Vectored Fms-Related Tyrosine Kinase 3 Ligand Inhibits CD34+ Progenitor Cell Engraftment in Humanized Mice

TitleAAV-Vectored Fms-Related Tyrosine Kinase 3 Ligand Inhibits CD34+ Progenitor Cell Engraftment in Humanized Mice
Authors
KeywordsCD34 + progenitor cells
Fms-related tyrosine kinase 3 ligand
humanized mouse
myeloid-derived immune suppressive cells
Issue Date2018
PublisherSpringer New York LLC.
Citation
Journal of Neuroimmune Pharmacology, 2018, v. 13 n. 4, p. 541-550 How to Cite?
AbstractHumanized mice have become useful animal models for HIV/AIDS. Since NOD.Cg-Prkdc scid Il2rgtm1Wjl/SzJ (NSG) mice allow the engraftment of primary human immune cells, we aim to determine the role of human Fms-related tyrosine kinase 3 ligand (hFlt3L), a major growth factor for dendritic cells (DCs), in regulating the differentiation of cord blood-derived CD34 + progenitor cells in this murine species. Soluble recombinant hFlt3L protein and AAV-vectored hFlt3L were administrated before or after human CD34 + progenitor cell transplantation, respectively. We then measured the peripheral levels of hFlt3L by ELISA. Meantime, reconstituted human immune cells were analyzed by flow cytometry over time. We found that without hFlt3L there were significantly increased types of human immune cells in NSG-huCD34 compared with NSG-huPBL mice but the frequency of human DCs remains low. Transient treatment with recombinant hFlt3L expanded human conventional CD1c + and CD141 + DCs as well as plasmacytoid DCs in humanized NSG-huCD34 mice. Surprisingly, however, the prolonged in vivo expression of AAV-vectored hFlt3L resulted in significant suppression of total human CD34 + cell engraftment and differentiation. The suppression occurred within 2 weeks when AAV-vectored hFlt3L was administered either before or after the transplantation of CD34 + progenitor cells, which was likely associated with the induction of murine myeloid-derived immune suppressive cells and reactive oxygen species in NSG-huCD34 mice. Since chronic HIV-1 patients displayed significantly high levels of hFlt3L expression, our findings may have implication to explore the role of prolonged hFlt3L in regulating the differentiation of human CD34 + progenitor cells in both NSG-huCD34 mice and infected people. [Figure not available: see fulltext.]. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.
Persistent Identifierhttp://hdl.handle.net/10722/273976
ISSN
2017 Impact Factor: 3.664
2015 SCImago Journal Rankings: 1.662
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLing, L-
dc.contributor.authorTang, X-
dc.contributor.authorHuang, X-
dc.contributor.authorLi, J-
dc.contributor.authorWang, H-
dc.contributor.authorChen, Z-
dc.date.accessioned2019-08-18T14:52:33Z-
dc.date.available2019-08-18T14:52:33Z-
dc.date.issued2018-
dc.identifier.citationJournal of Neuroimmune Pharmacology, 2018, v. 13 n. 4, p. 541-550-
dc.identifier.issn1557-1890-
dc.identifier.urihttp://hdl.handle.net/10722/273976-
dc.description.abstractHumanized mice have become useful animal models for HIV/AIDS. Since NOD.Cg-Prkdc scid Il2rgtm1Wjl/SzJ (NSG) mice allow the engraftment of primary human immune cells, we aim to determine the role of human Fms-related tyrosine kinase 3 ligand (hFlt3L), a major growth factor for dendritic cells (DCs), in regulating the differentiation of cord blood-derived CD34 + progenitor cells in this murine species. Soluble recombinant hFlt3L protein and AAV-vectored hFlt3L were administrated before or after human CD34 + progenitor cell transplantation, respectively. We then measured the peripheral levels of hFlt3L by ELISA. Meantime, reconstituted human immune cells were analyzed by flow cytometry over time. We found that without hFlt3L there were significantly increased types of human immune cells in NSG-huCD34 compared with NSG-huPBL mice but the frequency of human DCs remains low. Transient treatment with recombinant hFlt3L expanded human conventional CD1c + and CD141 + DCs as well as plasmacytoid DCs in humanized NSG-huCD34 mice. Surprisingly, however, the prolonged in vivo expression of AAV-vectored hFlt3L resulted in significant suppression of total human CD34 + cell engraftment and differentiation. The suppression occurred within 2 weeks when AAV-vectored hFlt3L was administered either before or after the transplantation of CD34 + progenitor cells, which was likely associated with the induction of murine myeloid-derived immune suppressive cells and reactive oxygen species in NSG-huCD34 mice. Since chronic HIV-1 patients displayed significantly high levels of hFlt3L expression, our findings may have implication to explore the role of prolonged hFlt3L in regulating the differentiation of human CD34 + progenitor cells in both NSG-huCD34 mice and infected people. [Figure not available: see fulltext.]. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.-
dc.languageeng-
dc.publisherSpringer New York LLC.-
dc.relation.ispartofJournal of Neuroimmune Pharmacology-
dc.rightsThis is a post-peer-review, pre-copyedit version of an article published in [insert journal title]. The final authenticated version is available online at: http://dx.doi.org/[insert DOI]-
dc.subjectCD34 + progenitor cells-
dc.subjectFms-related tyrosine kinase 3 ligand-
dc.subjecthumanized mouse-
dc.subjectmyeloid-derived immune suppressive cells-
dc.titleAAV-Vectored Fms-Related Tyrosine Kinase 3 Ligand Inhibits CD34+ Progenitor Cell Engraftment in Humanized Mice-
dc.typeArticle-
dc.identifier.emailChen, Z: zchenai@hku.hk-
dc.identifier.authorityChen, Z=rp00243-
dc.identifier.doi10.1007/s11481-018-9819-0-
dc.identifier.pmid30377944-
dc.identifier.scopuseid_2-s2.0-85055887600-
dc.identifier.hkuros301453-
dc.identifier.volume13-
dc.identifier.issue4-
dc.identifier.spage541-
dc.identifier.epage550-
dc.identifier.isiWOS:000449516700012-
dc.publisher.placeUnited States-

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