Flt3 ligand expands bona fide innate lymphoid cell precursors in vivo

• Published in: Scientific reports Vol. 8; no. 1; p. 154
• Main Authors: Parigi, Sara M., Czarnewski, Paulo, Das, Srustidhar, Steeg, Christiane, Brockmann, Leonie, Fernandez-Gaitero, Sara, Yman, Victor, Forkel, Marianne, Höög, Charlotte, Mjösberg, Jenny, Westerberg, Lisa, Färnert, Anna, Huber, Samuel, Jacobs, Thomas, Villablanca, Eduardo J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.01.2018; Nature Publishing Group
• Subjects: 13; 13/21; 13/31; 631/136/232/2058; 631/250/232/2058; 64; 64/60; Animals; Biomarkers; Bone marrow; Bone Marrow Cells - metabolism; Colitis; Disease Models, Animal; FLT3L protein; Humanities and Social Sciences; Humans; Immunity, Innate - genetics; Inflammatory bowel disease; Inflammatory bowel diseases; 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 cells; Lymphoid Progenitor Cells - immunology; Lymphoid Progenitor Cells - metabolism; Lymphopenia; Malaria; Medicin och hälsovetenskap; Melanoma, Experimental; Membrane Proteins - blood; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; multidisciplinary; Neoplasms - genetics; Neoplasms - immunology; Neoplasms - metabolism; Osteoprogenitor cells; Rodents; Science; Science (multidisciplinary); Small intestine; Transcription factors; Vector-borne diseases
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-18283-0

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 α4β7 + precursors in the adult murine bone marrow. Expanded Lin neg α4β7 + 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.