Forced-expression of Foxn1 in stromal cells maintains thymic architecture and thymopoiesis in aged mice (86.5)

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Abstract The thymus is the primary site for thymopoiesis and production of naïve T cells; however, thymic function declines with age. Thymopoiesis requires continuous thymic seeding by early T cell progenitors (ETP), a progeny of the bone marrow-derived lineage marker negative, Sca1pos, c-kitpos (LSK) progenitors that express Flt3 (LSK Flt3pos). A decrease in the frequency of ETP, and in the number of LSK Flt3pos with age has been implicated as a mechanism for the decline in thymopoiesis. We have shown that a decrease in thymocyte numbers occurs as early as 3m of age and correlates with a decrease in Foxn1 expression; however, a role for Foxn1 in thymopoiesis remains unknown. Here, we show that thymi of aged Foxn1 transgenic mice (Tg) have a higher number of thymocytes and ETP compared to aged wild type mice. Forced expression of Foxn1 also rescues aged-associated alterations of thymic architecture. Unexpectedly, we found that Foxn1 is over expressed in the bone marrow (BM). While the LSK and LSK Flt3pos are reduced in aged wild type mice, these populations remain unchanged in aged Foxn1Tg. Furthermore, the aged Foxn1 Tg also have a higher number of the lineage marker negative CD90.2pos CD2pos, a population absent in the Foxn1 mutated nude mice. Thus, our data suggest that expression of Foxn1 is critical for functional thymic and BM stromal cell niches required for the survival of T cell progenitors (NIA AG023809).