Molecular and biological role of the FOXP3 N-terminal domain in immune regulation by T regulatory/suppressor cells

Regulatory T (Treg) cells are essential in preventing the host from developing certain autoimmune diseases and limiting excessive immune responses against pathogens. The normal function of most Treg cells requires sustained expression of functional FOXP3, a member of the FOXP family transcription factors. FOXP3 is distinct from other subfamily members because of its unique proline rich amino (N)-terminal domain. Mutations in this region are occasionally identified in certain patients with X-linked autoimmunity-allergic dysregulation syndrome (XLAAD) and similar mutations also increase susceptibility of autoimmune diseases in rodent models. Previous analyses of the FOXP3 N-terminal domain revealed a role in nuclear import, interaction with other transcription factors, and as sites of specific post-translational modifications of FOXP3 that contribute to FOXP3 stability.