Enhancing T lineage production in aged mice: a novel function of Foxn1 in the bone marrow niche (P4475)

Abstract Foxn1 is essential for thymic organogenesis and T lymphopoiesis. While reduced Foxn1 expression results in a decline in T lymphopoiesis, overexpression of Foxn1 in the thymus of a transgenic mouse model (Foxn1Tg) attenuates the age-associated decline in T lymphopoiesis. T lymphopoiesis begins with ETP, derived from MPP in the BM. A decline in MPP and ETP numbers with age is thought to contribute to reduced T lymphopoiesis. Previously, we showed that reduced ETP number with age is attenuated in Foxn1Tg; whether the effect is initiated in the BM with MPP is not known. Here, we report that Foxn1 is expressed in Wt BM and over expressed in Foxn1Tg. With age, the number of MPP in Foxn1Tg was not reduced, and Foxn1Tg also have a larger pool of HSC. Furthermore, the Foxn1Tg BM is more efficient in generating MPP. In contrast to MPP, CLP and B lineage cell numbers were significantly lower in both young and aged Foxn1Tg compared to Wt. We identified a novel population of lineageneg/low, EpCAMpos, CD138neg cells as Foxn1-expressing BM cells that also express Delta-like 4. Thus, Foxn1 affects both T lymphopoiesis and hematopoiesis, suggesting that the Foxn1 BM niches function in skewing MPP development toward T lineage progenitors.