Flt3 ligand expands bona fide innate lymphoid cell precursors in vivo

Sci Rep. 2018 Jan 9;8(1):154. doi: 10.1038/s41598-017-18283-0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Bone Marrow Cells / metabolism
  • Disease Models, Animal
  • Humans
  • Immunity, Innate / genetics*
  • Inflammatory Bowel Diseases / genetics
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / metabolism
  • Inflammatory Bowel Diseases / pathology
  • Integrins / metabolism
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / metabolism*
  • Lymphoid Progenitor Cells / immunology
  • Lymphoid Progenitor Cells / metabolism*
  • Melanoma, Experimental
  • Membrane Proteins / blood
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mice
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / metabolism

Substances

  • Biomarkers
  • Integrins
  • Membrane Proteins
  • flt3 ligand protein
  • integrin alpha4beta7