References
Query Results -- Details
MGI Accession ID: MGI:3760052
J Number: J:125864
Other Accession IDs:
Title: RANK signals from CD4(+)3(-) inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla.
Authors: Rossi SW; Kim MY; Leibbrandt A; Parnell SM; Jenkinson WE; Glanville SH; McConnell FM; Scott HS; Penninger JM; Jenkinson EJ; Lane PJ; Anderson G
Journal: J Exp Med
Volume: 204
Issue: 6
Date: 2007 Jun 11
Year: 2007
Pages: 1267-72
Review Status: Peer Reviewed
Abstract:
Aire-expressing medullary thymic epithelial cells (mTECs) play a key role in preventing autoimmunity by expressing tissue-restricted antigens to help purge the emerging T cell receptor repertoire of self-reactive specificities. Here we demonstrate a novel role for a CD4(+)3(-) inducer cell population, previously linked to development of organized secondary lymphoid structures and maintenance of T cell memory in the functional regulation of Aire-mediated promiscuous gene expression in the thymus. CD4(+)3(-) cells are closely associated with mTECs in adult thymus, and in fetal thymus their appearance is temporally linked with the appearance of Aire(+) mTECs. We show that RANKL signals from this cell promote the maturation of RANK-expressing CD80(-)Aire(-) mTEC progenitors into CD80(+)Aire(+) mTECs, and that transplantation of RANK-deficient thymic stroma into immunodeficient hosts induces autoimmunity. Collectively, our data reveal cellular and molecular mechanisms leading to the generation of Aire(+) mTECs and highlight a previously unrecognized role for CD4(+)3(-)RANKL(+) inducer cells in intrathymic self-tolerance.
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