Flt3 ligand expands bona fide innate lymphoid cell precursors in vivo

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.

Reduced circulating dendritic cells in acute Plasmodium knowlesi and Plasmodium falciparum malaria despite elevated plasma Flt3 ligand levels

“…The plasma Flt3L increase observed in acute, uncomplicated falciparum or knowlesi malaria, are consistent with previous studies that found plasma Flt3L levels to be increased in clinical disease [19,20]. In children, Flt3L levels are significantly higher in severe malaria patients compared to uncomplicated malaria patients [19], however, Flt3L concentrations reported in uncomplicated malaria in children are lower than those recorded in adults in this study and by others [20].…”

“…In children with severe P. falciparum malaria, Plasmodium -induced Flt3L is reported to selectively stimulate the expansion of blood CD141 + DCs, but not other DC subsets [ 19 ]. Increased Flt3L is observed in adults with uncomplicated P. falciparum malaria [ 20 ], yet associations with DCs have not been investigated in adults. Here, plasma Flt3L and circulating DC numbers were quantified in adults experimentally infected with P. falciparum, and adults with clinical P. falciparum or P. knowlesi malaria to better understand the impact of a Plasmodium infection on circulating DC numbers and their association with plasma Flt3L levels.…”

Conserved transcriptomic profile between mouse and human colitis allows unsupervised patient stratification

“…Cell isolation from the colonic tissue was performed as previously described 56 with modifications. Briefly, tissues were open longitudinally, cut into 1-cm pieces, and washed with PBS.…”

Extensive dissemination and intraclonal maturation of HIV Env vaccine-induced B cell responses

“…Cell samples collected from different immune compartments were frozen in 90% heat-inactivated FBS and 10% DMSO (Sigma-Aldrich). Intestinal lamina propria cells were isolated from duodenum, ileum, or colon tissue of rhesus macaques, as previously described for murine tissue (Parigi et al, 2018). Briefly, 5-cm-long intestinal samples were placed in ice-cold PBS.…”