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.
Highlights
A common helper-like innate lymphoid precursor (CHILP) restricted to the innate lymphoid cells (ILC) lineage has been recently characterized
Concomitant with the expansion of CHILPs, PLZF+ ILC precursors (ILCP) numbers were increased in the bone marrow of B16-FMS-like tyrosine kinase 3 ligand (Flt3L) injected mice compared to its control counterpart (Fig. 1g and h)
Similar to what was observed with B16-Flt3L, Flt3L cytokine administration resulted in significant increase in CHILPs and ILCPs, but not of ILC2-committed precursors (ILC2P) numbers in the bone marrow over control mice (Supplementary Fig. 1c and d)
Summary
A common helper-like innate lymphoid precursor (CHILP) restricted to the innate lymphoid cells (ILC) lineage has been recently characterized. While CHILP numbers were stable during the course of DSS-induced colitis, they expanded following increased serum Flt3L levels in malariainfected mice, suggesting a role of the Flt3L-ILC axis in malaria. Innate lymphoid cells (ILCs) are a heterogeneous group of non-T, non-B lymphocytes comprising natural killer (NK) cells and distinct helper ILC subpopulations that differ from NK cells in terms of development and functions[7] Based on their functional and transcriptional activity, helper ILCs are classified into three main subsets: Group 1 ILCs (ILC1s) express the transcription factor T-bet, produce interferon-γ (IFN-γ) and tumor necrosis factor alpha (TNF-α) and participate in intracellular bacterial immunity[7]; Group 2 ILCs (ILC2s) express the transcription factor GATA-3, secrete interleukin (IL) -4, IL-5, IL-9 and IL-13 and play a role in immunity to helminths and allergic inflammations[8]; and Group 3 ILCs (ILC3s) express the transcription factor RORγt, www.nature.com/scientificreports/. In line with this, using different murine models of chronic intestinal inflammation, ILC3s have been shown to accumulate in the inflamed colon and subsequently promote pathology[20,21,22]
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