Lymphotoxin α fine-tunes T cell clonal deletion by regulating thymic entry of antigen-presenting cells.
Nat Commun
; 9(1): 1262, 2018 03 28.
Article
em En
| MEDLINE
| ID: mdl-29593265
ABSTRACT
Medullary thymic epithelial cells (mTEC) purge the T cell repertoire of autoreactive thymocytes. Although dendritic cells (DC) reinforce this process by transporting innocuous peripheral self-antigens, the mechanisms that control their thymic entry remain unclear. Here we show that mTEC-CD4+ thymocyte crosstalk regulates the thymus homing of SHPS-1+ conventional DCs (cDC), plasmacytoid DCs (pDC) and macrophages. This homing process is controlled by lymphotoxin α (LTα), which negatively regulates CCL2, CCL8 and CCL12 chemokines in mTECs. Consequently, Ltα-deficient mice have increased expression of these chemokines that correlates with augmented classical NF-κB subunits and increased thymic recruitment of cDCs, pDCs and macrophages. This enhanced migration depends mainly on the chemokine receptor CCR2, and increases thymic clonal deletion. Altogether, this study identifies a fine-tuning mechanism of T cell repertoire selection and paves the way for therapeutic interventions to treat autoimmune disorders.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Timo
/
Linfotoxina-alfa
/
Deleção Clonal
/
Células Apresentadoras de Antígenos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2018
Tipo de documento:
Article