| First Author | Wu W | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Pages | 44481 | PubMed ID | 28290551 |
| Mgi Jnum | J:275128 | Mgi Id | MGI:6296155 |
| Doi | 10.1038/srep44481 | Citation | Wu W, et al. (2017) Epithelial LTbetaR signaling controls the population size of the progenitors of medullary thymic epithelial cells in neonatal mice. Sci Rep 7:44481 |
| abstractText | The establishment of T cell central tolerance critically relies on the development and maintenance of the medullary thymic epithelial cells (mTECs). Disrupted signaling of lymphotoxin beta receptor (LTbetaR) results in dramatically reduced mTEC population. However, whether LTbetaR directly or indirectly control mTECs remains undetermined; how LTbetaR controls this process also remain unclear. In this study, by utilizing K14-Cre x Ltbr(fl/fl) conditional knockout (cKO) mice, we show that epithelial intrinsic LTbetaR was essential for the mTEC development postnatally. Mechanistically, LTbetaR did not directly impact the proliferation or survival of mTECs; the maturation of mTECs from MHC-II(lo) to MHC-II(hi) stage was also unaltered in the absence of LTbetaR; interestingly, the number of mTEC progenitors (Cld3,4(hi)SSEA-1(+)) was found significantly reduced in LTbetaR cKO mice at the neonatal stage, but not at E18.5. Consequently, epithelial deficiency of LTbetaR resulted in significant defect of thymic negative selection as demonstrated using OT-I and RIP-OVA transgenic mouse system. In summary, our study clarifies the epithelial intrinsic role of LTbetaR on mTEC development and function; more importantly, it reveals a previously unrecognized function of LTbetaR on the control of the size of mTEC progenitor population. |
