BibTex format
@article{Stadinski:2025:10.1038/s41590-025-02292-7,
author = {Stadinski, BD and Mills, EA and Humphries, PA and Cleveland, SB and Dow, P and Murakami, K and Li, YR and Murakami, M and Ono, M and Au-Yeung, BB and Morris, GP and Zúñiga-Pflücker, JC and Campbell, RA and Griffiths, ER and Huseby, ES and Lo, W-L},
doi = {10.1038/s41590-025-02292-7},
journal = {Nat Immunol},
title = {Age-dependent Zap70 expression in thymocytes regulates selection of the neonatal regulatory T cell repertoire.},
url = {http://dx.doi.org/10.1038/s41590-025-02292-7},
year = {2025}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - The Foxp3 regulatory T (Treg) cell repertoire carries age-dependent biases, with neonatal subsets enriched for highly self-reactive clones. However, the thymocyte features distinguishing neonatal from adult Treg selection remain unclear. Here, we show that neonatal double-positive mouse thymocytes, unlike their adult counterparts, fail to upregulate Zap70 during thymic selection, creating a calcium signaling bottleneck. This attenuated Zap70-dependent signaling limits negative selection, allowing highly self-reactive clones to evade deletion. Modulating Zap70 expression alters this balance; reducing Zap70 in adults rescues development of these clones, whereas increasing Zap70 in neonates enforces their deletion. Similarly, enhancing neonatal calcium signaling via increased LAT Y136-mediated PLCγ1 activation promotes clonal deletion. Analysis of pediatric human thymi reveals that ZAP70 expression remains low during the first year of life, aligning with the peak window for thymic Treg cell development. These findings suggest that age-dependent Zap70 expression regulates negative selection and thymic Treg cell development.
AU - Stadinski,BD
AU - Mills,EA
AU - Humphries,PA
AU - Cleveland,SB
AU - Dow,P
AU - Murakami,K
AU - Li,YR
AU - Murakami,M
AU - Ono,M
AU - Au-Yeung,BB
AU - Morris,GP
AU - Zúñiga-Pflücker,JC
AU - Campbell,RA
AU - Griffiths,ER
AU - Huseby,ES
AU - Lo,W-L
DO - 10.1038/s41590-025-02292-7
PY - 2025///
TI - Age-dependent Zap70 expression in thymocytes regulates selection of the neonatal regulatory T cell repertoire.
T2 - Nat Immunol
UR - http://dx.doi.org/10.1038/s41590-025-02292-7
UR - https://www.ncbi.nlm.nih.gov/pubmed/41057723
ER -