Flt3 ligand expands bona fide innate lymphoid cell precursors in vivo

TY - JOUR

T1 - Flt3 ligand expands bona fide innate lymphoid cell precursors in vivo

AU - Parigi, Sara M

AU - Czarnewski, Paulo

AU - Das, Srustidhar

AU - Steeg, Christiane

AU - Brockmann, Leonie

AU - Fernandez-Gaitero, Sara

AU - Yman, Victor

AU - Forkel, Marianne

AU - Höög, Charlotte

AU - Mjösberg, Jenny

AU - Westerberg, Lisa

AU - Färnert, Anna

AU - Huber, Samuel

AU - Jacobs, Thomas

AU - Villablanca, Eduardo J

PY - 2018/1/9

Y1 - 2018/1/9

N2 - 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)negα4β7+ precursors in the adult murine bone marrow. Expanded Linnegα4β7+ 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.

AB - 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)negα4β7+ precursors in the adult murine bone marrow. Expanded Linnegα4β7+ 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.

KW - Animals

KW - Biomarkers

KW - Bone Marrow Cells

KW - Disease Models, Animal

KW - Humans

KW - Immunity, Innate

KW - Inflammatory Bowel Diseases

KW - Integrins

KW - Lymphocyte Subsets

KW - Lymphoid Progenitor Cells

KW - Melanoma, Experimental

KW - Membrane Proteins

KW - Mice

KW - Neoplasms

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/s41598-017-18283-0

DO - 10.1038/s41598-017-18283-0

M3 - SCORING: Journal article

C2 - 29317685

VL - 8

SP - 154

JO - SCI REP-UK

JF - SCI REP-UK

SN - 2045-2322

IS - 1

ER -