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-kappaB activation. To test this hypothesis, 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-Foxj1-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-kappaB. Instead, CD2-Foxj1 transgenic mice exhibited a peripheral T cell lymphopenia, associated with an accumulation of mature single-positive thymocytes. Transgenic thymocytes demonstrated unimpaired lymphoid organ entry in adoptive transfer studies but demonstrated impaired thymic exodus in response to CCL19, apparently independent of CCR7, S1P1, and NF-kappaB. These findings 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.
Srivatsan
Subhashini
S
Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Peng
Stanford L
SL
D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity; D018801:CD2 Antigens / Q000235:genetics; D054415:Chemokine CCL19; D019742:Chemokines, CC; D002634:Chemotaxis, Leukocyte; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance; D008231:Lymphopenia / Q000209:etiology; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology*
C515460:CCL19 protein, human; D018801:CD2 Antigens; C515461:Ccl19 protein, mouse; D054415:Chemokine CCL19; D019742:Chemokines, CC; C481963:FOXJ1 protein, mouse; D051858:Forkhead Transcription Factors