| First Author | Lopes N | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 1262 |
| PubMed ID | 29593265 | Mgi Jnum | J:265728 |
| Mgi Id | MGI:6149242 | Doi | 10.1038/s41467-018-03619-9 |
| Citation | Lopes N, et al. (2018) Lymphotoxin alpha fine-tunes T cell clonal deletion by regulating thymic entry of antigen-presenting cells. Nat Commun 9(1):1262 |
| abstractText | 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 alpha (LTalpha), which negatively regulates CCL2, CCL8 and CCL12 chemokines in mTECs. Consequently, Ltalpha-deficient mice have increased expression of these chemokines that correlates with augmented classical NF-kappaB 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. |
