Publication
Molecular and functional evidence for activity of murine IL-7 on human lymphocytes
| Summary: | Although interleukin-7 (IL-7) is essential for human and murine lymphopoiesis and homeostasis, clear disparities between these species regarding the role of IL-7 during B-cell development suggest that other, subtler differences may exist. One basic unsolved issue of IL-7 biology concerns cross-species activity, because in contrast to the human ortholog, the ability of murine (m)IL-7 to stimulate human cells remains unresolved. Establishing whether two-way cross-species reactivity occurs is fundamental for evaluating the role of IL-7 in chimeric human-mouse models, which are the most versatile tools for studying human lymphoid development and disease in vivo. Here, we show that mIL-7 triggers the same signaling pathways as human (h)IL-7 in human T cells, promoting similar changes in viability, proliferation, size, and immunophenotype, even at low concentrations. This ability is not confined to T cells, because mIL-7 mediates cell growth and protects human B-cell precursors from dexamethasone-induced apoptosis. Importantly, endogenous mIL-7 produced in the mouse thymic microenvironment stimulates human T cells, because their expansion in chimeric fetal thymic organ cultures is inhibited by a mIL-7-specific neutralizing antibody. Our results demonstrate that mIL-7 affects human lymphocytes and indicate that mouse models of human lymphoid development and disease must integrate the biological effects of endogenous IL-7 on human cells. |
|---|---|
| Main Authors: | Barata, João T. |
| Other Authors: | Silva, Ana; Abecasis, Miguel; Carlesso, Nadia; Cumano, Ana; Cardoso, Angelo A. |
| Year: | 2006 |
| Country: | Portugal |
| Document type: | article |
| Access type: | restricted access |
| Associated institution: | Universidade de Lisboa |
| Language: | English |
| Origin: | Repositório da Universidade de Lisboa |
| _version_ | 1877774124390023168 |
|---|---|
| author | Barata, João T. |
| author2 | Silva, Ana Abecasis, Miguel Carlesso, Nadia Cumano, Ana Cardoso, Angelo A. |
| author2_role | author author author author author |
| author_facet | Barata, João T. Silva, Ana Abecasis, Miguel Carlesso, Nadia Cumano, Ana Cardoso, Angelo A. |
| author_role | author |
| contributor_name_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Barata, João T.\",\"Person.identifier.orcid\":\"0000-0002-4826-8976\",\"Person.identifier.researcherID\":\"D-9181-2015\",\"Person.identifier.scopusAuthorID\":\"7006937224\"},{\"Person.name\":\"Silva, Ana\"},{\"Person.name\":\"Abecasis, Miguel\"},{\"Person.name\":\"Carlesso, Nadia\"},{\"Person.name\":\"Cumano, Ana\"},{\"Person.name\":\"Cardoso, Angelo A.\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| datacite.creators.creator.creatorName.fl_str_mv | Barata, João T. Silva, Ana Abecasis, Miguel Carlesso, Nadia Cumano, Ana Cardoso, Angelo A. |
| datacite.date.Accepted.fl_str_mv | 2006-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2021-05-13T12:55:36Z |
| datacite.date.embargoed.fl_str_mv | 2021-05-13T12:55:36Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_16ec |
| datacite.titles.title.fl_str_mv | Molecular and functional evidence for activity of murine IL-7 on human lymphocytes |
| dc.contributor.none.fl_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| dc.creator.none.fl_str_mv | Barata, João T. Silva, Ana Abecasis, Miguel Carlesso, Nadia Cumano, Ana Cardoso, Angelo A. |
| dc.date.Accepted.fl_str_mv | 2006-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2021-05-13T12:55:36Z |
| dc.date.embargoed.fl_str_mv | 2021-05-13T12:55:36Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10451/47833 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Elsevier |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_16ec |
| dc.title.fl_str_mv | Molecular and functional evidence for activity of murine IL-7 on human lymphocytes |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Although interleukin-7 (IL-7) is essential for human and murine lymphopoiesis and homeostasis, clear disparities between these species regarding the role of IL-7 during B-cell development suggest that other, subtler differences may exist. One basic unsolved issue of IL-7 biology concerns cross-species activity, because in contrast to the human ortholog, the ability of murine (m)IL-7 to stimulate human cells remains unresolved. Establishing whether two-way cross-species reactivity occurs is fundamental for evaluating the role of IL-7 in chimeric human-mouse models, which are the most versatile tools for studying human lymphoid development and disease in vivo. Here, we show that mIL-7 triggers the same signaling pathways as human (h)IL-7 in human T cells, promoting similar changes in viability, proliferation, size, and immunophenotype, even at low concentrations. This ability is not confined to T cells, because mIL-7 mediates cell growth and protects human B-cell precursors from dexamethasone-induced apoptosis. Importantly, endogenous mIL-7 produced in the mouse thymic microenvironment stimulates human T cells, because their expansion in chimeric fetal thymic organ cultures is inhibited by a mIL-7-specific neutralizing antibody. Our results demonstrate that mIL-7 affects human lymphocytes and indicate that mouse models of human lymphoid development and disease must integrate the biological effects of endogenous IL-7 on human cells. |
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| funding.funder.identifier_str_mv | http://doi.org/10.13039/501100001871 http://doi.org/10.13039/501100001871 |
| funding.funder.name_str_mv | Fundação para a Ciência e a Tecnologia Fundação para a Ciência e a Tecnologia |
| funding.identifier_str_mv | SFRH/BD/18388/2004 POCTI/CBO/34914/2000 |
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| person_str_mv | Barata, João T. Barata, João T. http://orcid.org/0000-0002-4826-8976 0000-0002-4826-8976 Silva, Ana Abecasis, Miguel Carlesso, Nadia Cumano, Ana Cardoso, Angelo A. |
| publishDate | 2006 |
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| spelling | engElsevierpt_PTAlthough interleukin-7 (IL-7) is essential for human and murine lymphopoiesis and homeostasis, clear disparities between these species regarding the role of IL-7 during B-cell development suggest that other, subtler differences may exist. One basic unsolved issue of IL-7 biology concerns cross-species activity, because in contrast to the human ortholog, the ability of murine (m)IL-7 to stimulate human cells remains unresolved. Establishing whether two-way cross-species reactivity occurs is fundamental for evaluating the role of IL-7 in chimeric human-mouse models, which are the most versatile tools for studying human lymphoid development and disease in vivo. Here, we show that mIL-7 triggers the same signaling pathways as human (h)IL-7 in human T cells, promoting similar changes in viability, proliferation, size, and immunophenotype, even at low concentrations. This ability is not confined to T cells, because mIL-7 mediates cell growth and protects human B-cell precursors from dexamethasone-induced apoptosis. Importantly, endogenous mIL-7 produced in the mouse thymic microenvironment stimulates human T cells, because their expansion in chimeric fetal thymic organ cultures is inhibited by a mIL-7-specific neutralizing antibody. Our results demonstrate that mIL-7 affects human lymphocytes and indicate that mouse models of human lymphoid development and disease must integrate the biological effects of endogenous IL-7 on human cells.application/pdfpt_PTMolecular and functional evidence for activity of murine IL-7 on human lymphocytesPersonalBarata, João T.DSpacehttp://dspace.org/items/06f27f7f-1c6c-4c03-a70d-52f8a388bd3bDSpacehttp://dspace.org/items/06f27f7f-1c6c-4c03-a70d-52f8a388bd3bBarataJoãoORCIDhttp://orcid.org0000-0002-4826-8976Researcher IDhttps://www.researcherid.comD-9181-2015Scopus Author IDhttps://www.scopus.com7006937224Silva, AnaAbecasis, MiguelCarlesso, NadiaCumano, AnaCardoso, Angelo A.HostingInstitutionOrganizationalRepositório Científico de Acesso Aberto da ULisboae-mailmailto:repositorio@ulisboa.ptrepositorio@ulisboa.ptISSNIsPartOf0301-472XDOIIsPartOf10.1016/j.exphem.2006.05.0012021-05-13T12:55:36Z20062006-01-01T00:00:00ZHandlehttp://hdl.handle.net/10451/47833http://purl.org/coar/access_right/c_16ecrestricted access594572 bytesFundação para a Ciência e a TecnologiaIL-7- AND PI3K-MEDIATED SIGNALING IN T-CELL LEUKEMIA: THE ROLE OF EXTERNAL AND CELL-AUTONOMOUS SIGNALS IN TUMORIGENESISinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F18388%2F2004/PTSFRH/BD/18388/2004Crossref Funder IDhttp://doi.org/10.13039/501100001871Fundação para a Ciência e a TecnologiaTARGETING SIGNALING PATHWAYS AS THERAPY FOR HUMAN CANCERinfo:eu-repo/grantAgreement/FCT/POCI/POCTI%2FCBO%2F34914%2F2000/PTPOCTI/CBO/34914/2000POCICrossref Funder IDhttp://doi.org/10.13039/501100001871literaturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_16ecapplication/pdffulltexthttps://repositorio.ulisboa.pt/bitstreams/213a34a0-ad1a-4926-96e7-b87ec26515fe/downloadExperimental Hematology34911321141 |
| spellingShingle | Molecular and functional evidence for activity of murine IL-7 on human lymphocytes Barata, João T. |
| status | SINGLETON |
| title | Molecular and functional evidence for activity of murine IL-7 on human lymphocytes |
| title_full | Molecular and functional evidence for activity of murine IL-7 on human lymphocytes |
| title_fullStr | Molecular and functional evidence for activity of murine IL-7 on human lymphocytes |
| title_full_unstemmed | Molecular and functional evidence for activity of murine IL-7 on human lymphocytes |
| title_short | Molecular and functional evidence for activity of murine IL-7 on human lymphocytes |
| title_sort | Molecular and functional evidence for activity of murine IL-7 on human lymphocytes |
| url | http://hdl.handle.net/10451/47833 |
| visible | 1 |