RANK signals from CD4(+)3(-) inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla
- Author(s)
- Rossi, SW; Kim, MY; Leibbrandt, A; Parnell, SM; Jenkinson, WE; Glanville, SH; McConnell, FM; Scott, HS; Penninger, JM; Jenkinson, EJ; Lane, PJL; Anderson, G;
- Details
- Publication Year 2007-06-11,Volume 204,Issue #6,Page 1267-1272
- Journal Title
- JOURNAL OF EXPERIMENTAL MEDICINE
- Publication Type
- Journal Article
- 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.
- Publisher
- ROCKEFELLER UNIV PRESS
- Keywords
- PROMISCUOUS GENE-EXPRESSION; CD4(+)CD3(-) CELLS; AUTOIMMUNITY; STROMA; MATURATION; TOLERANCE; LIGAND; OX40
- Publisher's Version
- https://doi.org/10.1084/jem.20062497
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2007-06-11 12:00:00