Flt3l-flox Mouse

Flt3l, encoded by FLT3LG, is a hematopoietic factor also known as FMS-related tyrosine kinase 3 ligand. It acts on Flt3-expressing multipotent progenitors and common lymphoid progenitors. The Flt3/Flt3L axis is mainly involved in the generation of conventional DCs (cDCs) and plasmacytoid DCs (pDCs), and Flt3 signaling through PI3K and mTOR may affect the function of mature DCs [2].

In mice, Flt3l is essential for the development of natural killer (NK) cells, B cells, and dendritic cells (DCs) [1]. In humans, three individuals homozygous for a loss-of-function FLT3LG variant had hypoplastic bone marrow, low levels of hematopoietic progenitors, and reduced counts of B cells, monocytes, and DCs in the blood [1]. Maternal low-fiber diet in mice led to reduced neonatal intestinal epithelial cell secretion of Flt3L, impairing pDC hematopoiesis and increasing LRI severity in offspring [3].

In cancer research, in vitro experiments showed that the combination of Flt3L, LIF, and IL-10 promoted the selective development of ESAMlow cDC2B from murine bone marrow [5]. Also, Flt3L therapy increased all cDC subsets in orthotopic breast and lung cancer models in mice, but did not reduce tumor growth [4].

In conclusion, Flt3l is crucial for the development of multiple hematopoietic lineages, including B cells and DCs in both mice and humans. In mice, it also impacts NK cell development. Its role in diseases, especially in relation to immune responses in cancer and infectious diseases, has been revealed through various mouse models. Understanding Flt3l can provide insights into hematopoietic development and potential immunotherapy strategies.