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Publication : Premature expression of Foxp3 in double-negative thymocytes.

First Author  Barra MM Year  2015
Journal  PLoS One Volume  10
Issue  5 Pages  e0127038
PubMed ID  25978037 Mgi Jnum  J:235318
Mgi Id  MGI:5796075 Doi  10.1371/journal.pone.0127038
Citation  Barra MM, et al. (2015) Premature expression of Foxp3 in double-negative thymocytes. PLoS One 10(5):e0127038
abstractText  Peripheral immune regulation depends on the generation of thymic-derived regulatory T (tTreg) cells to maintain self-tolerance and to counterbalance overshooting immune responses. The expression of the Treg lineage defining transcription factor Foxp3 in developing tTreg cells depends on TCR signaling during the thymic selection process of these T cells. In this study, we surprisingly identify Foxp3+ immature thymocytes at the double-negative (DN) stage in transcription factor 7 (Tcf7)-deficient mice. These Foxp3+ cells did not express a TCR (beta or gammadelta chains), CD3 or CD5 and therefore these cells were true DN cells. Further investigation of this phenomenon in a transgenic TCR model showed that Foxp3-expressing DN cells could not respond to TCR stimulation in vivo. These data suggest that Foxp3 expression in these DN cells occurred independently of TCR signaling. Interestingly, these Foxp3+ DN cells were located in a transition state between DN1 and DN2 (CD4-CD8-CD3-TCR-CD44highCD25low). Our results indicate that Tcf7 is involved in preventing the premature expression of Foxp3 in DN thymocytes.
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