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Flt3 ligand expands bona fide innate lymphoid cell precursors in vivo
Karolinska Institute, Sweden; University Hospital, Sweden.
Karolinska Institute, Sweden; University Hospital, Sweden.
Karolinska Institute, Sweden; University Hospital, Sweden.
Bernhard Nocht Institute Trop Med, Germany.
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 154Article in journal (Refereed) Published
Abstract [en]

A common helper-like innate lymphoid precursor (CHILP) restricted to the innate lymphoid cells (ILC) lineage has been recently characterized. While specific requirements of transcription factors for CHILPs development has been partially described, their ability to sense cytokines and react to peripheral inflammation remains unaddressed. Here, we found that systemic increase in Flt3L levels correlated with the expansion of Lineage (Lin)(neg)alpha 4 beta 7(+) precursors in the adult murine bone marrow. Expanded Lin(neg)alpha 4 beta 7(+) precursors were bona fide CHILPs as seen by their ability to differentiate into all helper ILCs subsets but cNK in vivo. Interestingly, Flt3L-expanded CHILPs transferred into lymphopenic mice preferentially reconstituted the small intestine. While we did not observe changes in serum Flt3L during DSS-induced colitis in mice or plasma from inflammatory bowel disease (IBD) patients, elevated Flt3L levels were detected in acute malaria patients. Interestingly, while CHILP numbers were stable during the course of DSS-induced colitis, they expanded following increased serum Flt3L levels in malaria-infected mice, hence suggesting a role of the Flt3L-ILC axis in malaria. Collectively, our results indicate that Flt3L expands CHILPs in the bone marrow, which might be associated with specific inflammatory conditions.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2018. Vol. 8, article id 154
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Immunology in the medical area
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URN: urn:nbn:se:liu:diva-144558DOI: 10.1038/s41598-017-18283-0ISI: 000419659600035PubMedID: 29317685OAI: oai:DiVA.org:liu-144558DiVA, id: diva2:1178287
Note

Funding Agencies|Swedish Research Council VR grant [K2015-68X-22765-01-6]; FORMAS [2016-00830]; Wallenberg Academy Fellow (WAF) program

Available from: 2018-01-29 Created: 2018-01-29 Last updated: 2018-02-21

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Division of Surgery, Orthopedics and OncologyFaculty of Medicine and Health Sciences
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