2. Academic Validation
  3. FOXN1 mutation abrogates prenatal T-cell development in humans

FOXN1 mutation abrogates prenatal T-cell development in humans

  • J Med Genet. 2011 Jun;48(6):413-6. doi: 10.1136/jmg.2011.089532.
I Vigliano 1,  M Gorrese,  A Fusco,  L Vitiello,  S Amorosi,  L Panico,  M V Ursini,  G Calcagno,  L Racioppi,  L Del Vecchio,  C Pignata
Affiliations

Affiliation

  • 1 Department of Pediatrics, 'Federico II' University, Via Pansini, 5, Naples 80131, Italy. [email protected]
PMID: 21507891 DOI: 10.1136/jmg.2011.089532
Abstract

Background: The transcription factor FOXN1 is implicated in the differentiation of thymic and skin epithelial cells, and alterations in it are responsible for the Nude/SCID phenotype. During a genetic counselling programme offered to couples at risk in a community where a high frequency of mutated FOXN1 had been documented, the identification of a human FOXN1(-/-) fetus gave the unique opportunity to study T cell development in utero.

Results: Total blockage of CD4(+) T cell maturation and severe impairment of CD8(+) cells were documented. Evaluation of the variable-domain β-chain (Vβ) families' usage among T lymphocytes revealed that the generation of T cell receptor (TCR) diversity occurred to some extent in the FOXN1(-/-) fetus, although it was impaired compared with the control. A few non-functional CD8(+) cells, mostly bearing TCRγδ in the absence of CD3, were found.

Discussion: FOXN1 is crucial for in utero T cell development in humans. The identification of a limited number of CD8(+) cells suggests an extrathymic origin for these cells, implying FOXN1-independent lymphopoiesis.

Figures