title: SATB1 Plays a Critical Role in Establishment of Immune Tolerance.
abstract: Special AT-rich 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 SATB1 in T cell development have not been well clarified. In this study, we generated and analyzed SATB1 conditional knockout (cKO) mice, in which the SATB1 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 also found that SATB1 cKO mice developed autoimmune diseases within 16 wk after birth. In SATB1 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 SATB1 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 SATB1. In addition, negative selection during T cell development in the thymus was severely impaired in SATB1 deficient mice. These results suggest that SATB1 plays an essential role in establishment of immune tolerance.
authors.affiliation: Department of Molecular Immunology, Toho University School of Medicine, Tokyo 143-8540, Japan; Department of Immunology, Duke University Medical Center, Durham, NC 27710; and motonari.kondo@med.toho-u.ac.jp yurikota@med.toho-u.ac.jp.
authors.forename: Motonari
authors.identifier: http://orcid.org/0000-0002-1565-8804
authors.initials: M
authors.lastname: Kondo
authors.affiliation: Department of Molecular Immunology, Toho University School of Medicine, Tokyo 143-8540, Japan; motonari.kondo@med.toho-u.ac.jp yurikota@med.toho-u.ac.jp.
authors.forename: Yuriko
authors.identifier: http://orcid.org/0000-0002-9278-7677
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Molecular Immunology, Toho University School of Medicine, Tokyo 143-8540, Japan;
authors.forename: Taku
authors.initials: T
authors.lastname: Kuwabara
authors.affiliation: Department of Molecular Immunology, Toho University School of Medicine, Tokyo 143-8540, Japan;
authors.forename: Taku
authors.identifier: http://orcid.org/0000-0001-6440-5566
authors.initials: T
authors.lastname: Naito
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, CA 94720.
authors.forename: Terumi
authors.identifier: http://orcid.org/0000-0002-5988-0669
authors.initials: T
authors.lastname: Kohwi-Shigematsu
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710; and.
authors.forename: Akiko
authors.identifier: http://orcid.org/0000-0003-4741-4705
authors.initials: A
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000276:immunology*; D007150:Immunohistochemistry; D036961:Matrix Attachment Region Binding Proteins / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D013950:Thymus Gland / Q000254:growth & development / Q000276:immunology
chemical_list: D036961:Matrix Attachment Region Binding Proteins; C469541:Satb1 protein, mouse