Forkhead transcription factors in T lymphocytes

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DESCRIPTION (provided by applicant): The Fox/forkhead family encompasses an ever-growing number of helix-loop-helix transcription factors that participate in diverse biological systems. We describe here an immune role for Foxj1, a Fox family member originally characterized for its role in ciliated epithelial cells. In its absence, helper T (Th) cells are characterized by Th1-skewed hyperproliferation, associated with multi-system auto-inflammation. As such, Foxj1 plays a critical role in the maintenance of T cell quiescence and/or immune tolerance, but we know relatively little about its mechanism of action, as well as its contextual importance in T cell activation. We therefore propose in this application to delve further into the role of Foxj1 in T cell biology - in particular to examine more completely its role in Th proliferation and activation, to determine more fully its relevance to autoimmunity, and to elucidate the molecular pathway in which it operates.