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  • Lindau, RobertLinköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten (author)

Decidual stromal cells support tolerance at the human foetal-maternal interface by inducing regulatory M2 macrophages and regulatory T-cells

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • Elsevier Ireland Ltd,2021
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:liu-178536
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-178536URI
  • https://doi.org/10.1016/j.jri.2021.103330DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:147135304URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Funding Agencies|Swedish Research CouncilSwedish Research CouncilEuropean Commission [201901311, 201802776]; Medical Research Council of Southeast SwedenUK Research & Innovation (UKRI)Medical Research Council UK (MRC); ALF grants; Linkodping University; Cancer Society in Stockholm [141193]; Swedish Cancer Foundation [CAN 2014/793]; Swedish Childhood Cancer FoundationEuropean Commission [PR2015-0059]; Karolinska InstitutetKarolinska Institutet
  • During pregnancy, the semi-allogeneic nature of the foetus requires maternal immune adaption and acquisition of tolerance at the foetal-maternal interface. Macrophages with regulatory properties and regulatory T (Treg) cells are central in promoting foetal tolerance and are enriched in the decidua (the uterine endometrium during pregnancy). Although tissue-resident decidual stromal cells (DSC) have been implicated in regulatory functions, it is not known if they are able to induce the regulatory phenotype of macrophages and T-cells. In this study we report that maternally derived DSC are able to induce homeostatic M2 macrophages and Treg cells. CD14+ monocytes and CD4+ T-cells from healthy non-pregnant women were cultured in the presence or absence of conditioned medium (CM) from DSC isolated from 1st trimester and term placentas. DSC-CM alone was able to promote the survival of macrophages and to induce a regulatory CD14brightCD163+CD209+CD86dim phenotype, typical for decidual macrophages and similar to that induced by M-CSF. Interestingly, DSC-CM was also able to overrule the pro-inflammatory effects of GM-CSF by upregulating CD14, CD163 and CD209. Protein-profiling showed that M-CSF was secreted by DSC, and blocking of M-CSF partially reversed the M2 phenotype and reduced viability. DSC-CM also expanded CD25brightFoxp3+ Treg cells, an expansion that was abolished by a SMAD3-inhibitor, indicating the contribution of TGF-beta signaling. In conclusion, our findings collectively emphasize the role of tissue-resident stromal cells in shaping the tolerogenic environment at the foetal-maternal interface.

Subject headings and genre

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  • Vondra, SigridLinköpings universitet,Medicinska fakulteten,Institutionen för biomedicinska och kliniska vetenskaper,Med Univ Vienna, Austria(Swepub:liu)sigvo50 (author)
  • Spreckels, JohanneLinköpings universitet,Medicinska fakulteten,Institutionen för biomedicinska och kliniska vetenskaper,Univ Med Ctr Groningen, Netherlands(Swepub:liu)johsp90 (author)
  • Solders, M.Karolinska Inst, Sweden; Karolinska Univ Hosp Huddinge, Sweden (author)
  • Svensson-Arvelund, Judit,1982-Linköpings universitet,Avdelningen för molekylär medicin och virologi,Medicinska fakulteten(Swepub:liu)judsv82 (author)
  • Berg, GöranLinköpings universitet,Avdelningen för barns och kvinnors hälsa,Medicinska fakulteten,Region Östergötland, Kvinnokliniken US(Swepub:liu)gorbe09 (author)
  • Pollheimer, J.Med Univ Vienna, Austria (author)
  • Kaipe, H.Karolinska Institutet,Karolinska Inst, Sweden; Karolinska Univ Hosp Huddinge, Sweden (author)
  • Jenmalm, MariaLinköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten(Swepub:liu)marje18 (author)
  • Ernerudh, JanLinköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten,Region Östergötland, Klinisk immunologi och transfusionsmedicin(Swepub:liu)janer15 (author)
  • Linköpings universitetAvdelningen för inflammation och infektion (creator_code:org_t)

Related titles

  • In:Journal of Reproductive Immunology: Elsevier Ireland Ltd1460165-03781872-7603

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