Critical role of FLT3 ligand in IL-7 receptor-independent T lymphopoiesis and regulation of lymphoid-primed multipotent progenitors
2007 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 110, no 8, 2955-2964 p.Article in journal (Refereed) Published
The molecular pathways regulating lymphoid priming, fate, and development of multipotent bone marrow (BM) stem/progenitor cells that continuously replace thymic progenitors remain largely unknown. Herein, we show that fms-like tyrosine kinase 3 (Flt3) ligand (Fl)–deficient mice have distinct reductions in the earliest thymic progenitors in fetal, postnatal, and adult thymus. A critical role of FL in thymopoiesis was particularly evident in the absence of interleukin-7 receptor (IL-7R) signaling. Fl–/–Il-7r–/– mice have extensive reductions in fetal and postnatal thymic progenitors that result in a loss of active thymopoiesis in adult mice, demonstrating an indispensable role of FL in IL-7R–independent fetal and adult T lymphopoiesis. Moreover, we establish a unique and critical role of FL, distinct from that of IL-7R, in regulation of the earliest lineage-negative (Lin–) Lin–SCA1+KIT+ (LSK) FLT3hi lymphoid-primed multipotent progenitors in BM, demonstrating a key role of FLT3 signaling in regulating the very earliest stages of lymphoid progenitors.
Place, publisher, year, edition, pages
2007. Vol. 110, no 8, 2955-2964 p.
National CategoryMedical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-39976DOI: 10.1182/blood-2006-10-054726Local ID: 51895OAI: oai:DiVA.org:liu-39976DiVA: diva2:260825