Karla Wiehagen
Research Interests: Transplantation and Tolerance, Cell and Developmental Biology of the Immune System
Research Description: Our work is focused on understanding the role of the forkhead transcription factor Foxp4 in lymphocyte development and function. Forkhead family members Foxp1 and Foxp3 have a role in regulating the development and function of lymphocytes. But, while Foxp4 is expressed in lymphocytes, its function is unknown. Previous work in our lab has shown that Foxp4 expression is dynamically regulated through stages of thymic maturation, suggesting a role in T cell development. Because germline Foxp4 knockout animals are embryonic lethal due to defects in heart and lung development, we used tissue specific conditional deletion to examine the effect of removing Foxp4 from the hematopoietic lineage. T cell development is normal, yet T cell function is enhanced. Despite normal cell surface phenotype and cellularity, Foxp4 conditional knockout (cKO) T cells are more responsive to in vitro stimulation than littermate controls. Specifically, a higher frequency of Foxp4 cKO CD4 and CD8 T cells produce cytokines in response to T cell receptor stimulation, suggesting Foxp4 targets are important for modulating effector function programs in peripheral T cells. Like other Foxp family members, Foxp4 appears to have a role in regulating immune responses, by constraining T cell effector functions.