1º Título do projeto: Identifying Thymic Epithelial Cell Progenitors.
2º Investigador responsável: Nuno Alves
3º Sumário do projeto
T cells represent an effective arm of the immune system and their development takes
place in the thymus. The thymus contains specialized types of thymic epithelial cells
(TECs) that provide a variety of specialized microenvironments that support T cell
differentiation and establish T cell self-tolerance. Thymic cortical (cTECs) and medullary
(mTECs) epithelial cells form two functionally distinct microenvironments, and derive
from a common bipotent TEC progenitor. While the molecular basis of mTEC maturation
is partially elucidated, the differentiation of cTECs remains poorly defined. Current
strategies to boost thymic activity include sex steroid ablation and growth factor
supplementation. Alternative approaches may include activating TEC progenitors to
mediate thymic regeneration. Whist evidence indicates the existence of a bipotent TEC
progenitor in the adult thymus, the identity of these cells remains elusive.
Here, we will employ a series of reporter mice, which identify specialized TEC subsets,
to (I) identify TEC precursors, (II) study their clonogenic potential and (III) analyzing the
cellular and molecular networks controlling their differentiation into mature TECs
lineages. Knowledge in this area may provide novel insights to be integrated into
therapeutics to boost and regenerate thymic function in immunodeficient patients and in
the elderly.
4º Está associado a um projeto financiado: Sim. FCT PTDC/.SAU-IMU/117057/2010
5º Referências bibliográficas
1. Ribeiro AR, Rodrigues P, Meireles C, Di Santo JP, Alves NL 2013. Thymocyte selection regulates the
homeostasis of IL-7-expressing thymic cortical epithelial cells in vivo. J Immunol 2013 Aug; 191(3). Epub
2013 Jun 21.
2. Alves NL, Huntington ND, Mention JJ, Richard-Le Goff O, Di Santo JP. 2010. Cutting Edge: a
Thymocyte-thymic epithelial cell cross-talk dynamically regulates intrathymic IL-7 expression in vivo. J
Immunol 184: 5949-53.
3. Alves NL, Huntington ND, Rodewald HR, Di Santo JP. 2009. Thymic epithelial cells: the multi-tasking
framework of the T cell "cradle". Trends Immunol 30: 468-74.
4. Alves NL, Goff OR, Huntington ND, Sousa AP, Ribeiro VS, Vives FL, Peduto L, Chidgey A, Cumano
A, Boyd R, Eberl G, Di Santo JP. 2009. Characterization of the thymic IL-7 niche in vivo. Proc Natl Acad
SciU S A 2009 Feb 3;106(5):1512-1517.