SATB1 Plays a Critical Role in Establishment of Immune Tolerance.

Special AT-rieh sequence binding protein 1 (SATB1) is a genome organizer that is expressed by T cells. T cell development is severely impaired in SATB1 null mice; however, because SATB1 null mice die by 3 wk of age, the roles of SATBI in T cell development have not been well clarified. In this study, we generated and analyzed SATBI conditional knockout (cKO) mice, in which the SATBI gene was deleted from all hematopoietic cells. T cell numbers were reduced in these mice, mainly because of a deficiency in positive selection at the CD4+CD8+ double-positive stage during T cell development in the thymus. We alsofound that SATBI cKO mice developed autoimmune diseases within 16 wk after birth. In SATBI cKO mice, the numbers of Foxp3+ regulatory T (Treg) cells were significantly reduced at 2 wk of age compared with wild-type littermates. Although the numbers gradually increased upon aging, Treg cells in SATBI cKO mice were still less than those in wild-type littermates at adulthood. Suppressive functions of Treg cells, which play a major role in establishment of peripheral tolerance, were also affected in the absence of SATBI. In addition, negative selection during T cell development in the thymus was severely impaired in SATBI deficient mice. These results suggest that SATBI plays an essential role in establishment of immune tolerance. [ABSTRACT FROM AUTHOR]