Cutting edge: Foxj1 protects against autoimmunity and inhibits thymocyte egress

Previous studies suggest that the forkhead transcription factor Foxj1 inhibits spontaneous autoimmunity in part by antagonizing NF-kappa B activation. To test this hypothesise we ectopically expressed Foxj1 in the T cells of lupus-prone MRL/lpr mice by backcrossing a CD2-Foxj1 transgene against the MRL/lpr background Strikingly, CD2-Fox1-MRL/lpr animals showed a significant reduction in lymphadenopathy, pathogenic autoantibodies, and end-organ disease-but surprisingly, reversion of autoimmunity was not attributable to modulation of NF-kappa B. Instead, CD2-Foxj1 transgenic mice exbibited a peripheral T cell lymphopenia, associated with an accumulation of mature single-positive thymocytes. Transgenic thymocytes demonstrated unimpaired impboid organ entry in adoptive transfer studies but demonstrated impaired thymic exodus in response to CCL19, apparently independent of CCR7, S1P1, and NF-kappa B. Thesefindings confirm the importance of Foxj1 in the regulation of T cell tolerance but furthermore suggest a novel and specific role for Foxj1 in regulating thymic egress.