ナイトウ　タク   Naito Taku   内藤　拓    所属   東邦大学  医学部 医学科    職種   准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Crucial Roles of SATB1 in Regulation of Thymocyte Migration after Positive Selection
掲載誌名	正式名：Journal of Immunology 略　 称：J Immunol ISSNコード：00221767
掲載区分	国外
出版社	American Society of Immunologists
国際共著	国際共著
著者・共著者	Taku Naito, Marii Ise, Yuriko Tanaka, Terumi Kohwi-Shigematsu, Motonari Kondo
担当区分	筆頭著者,責任著者
発行年月	2023/05/31
概要	Double-positive thymocytes that have passed positive selection migrate from the cortex to the medulla, where negative selection and the development of thymic regulatory T cells (tTregs) take place. Medullary thymic epithelial cells (mTECs) play important roles in these selections, and their differentiation and maintenance depend on interaction with positively selected CD4+ single-positive cells. Therefore, migration and differentiation after positive selection must be coordinated to establish immune tolerance. However, the regulatory mechanisms of these processes are not fully understood. SATB1 is a genome organizer highly expressed in double-positive thymocytes, and SATB1 deletion causes various defects in T-cell development, including impaired positive and negative selection and tTreg differentiation. Here, we show that SATB1 is critical for temporally coordinated thymocyte trafficking after positive selection in mice. Satb1 knockout (ΔSatb1) led to precocious thymic egress caused by augmented S1pr1 upregulation in positively selected thymocytes, accompanied by lower induction of Ccr7, Tnfsf11, and Cd40lg. Altered thymocyte trafficking and functionality affected the differentiation of mTECs and, in turn, tTreg differentiation. Thus, SATB1 is required to establish immune tolerance, at least in part, by ensuring timely thymic egress and mTEC differentiation.
DOI	10.4049/jimmunol.2200572
PMID	37256264