FOXN1 mutation abrogates prenatal T-cell development in humans

Ilaria Vigliano (1) , Marisa Gorrese (2) , Anna Fusco (1) , Laura Vitiello (2) , Stefania Amorosi (1) , L. Panico (3) , M.V. Ursini (4) , Giuseppe Calcagno (2) , Luigi Racioppi (2) , Luigi del Vecchio (2) , Claudio Pignata (1)

1 Department of Pediatrics,
2 University of Naples Federico II = Università degli studi di Napoli Federico II
3 Unit of Pathology, National Relevance Hospital
4 Institute of Genetics and Biophysics

The transcription factor FOXN1 is implicated in the differentiation of thymic and skin epithelial cells and its alterations are responsible for the Nude/SCID phenotype. During a genetic counseling program offered to couples at risk in the community where a high frequency of mutated FOXN1 has been documented, the identification of a human FOXN1-/- fetus gave the unique opportunity to study T-cell development in utero. A total blockage of CD4+ T-cell maturation and a severe impairment of CD8+ cells were documented. The evaluation of the variable-domain β-chain (Vβ) families' usage among T lymphocytes revealed that the generation of TCR diversity occurred at some extent in the FOXN1-/- fetus, although it was impaired compared to the control. A few non-functional CD8+ cells, mostly bearing TCRγδ in the absence of CD3 were found. 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, thus implying a FOXN1-independent lymphopoiesis.

Mots clés: Clinical genetics; Immunology (including allergy)

Ilaria Vigliano, Marisa Gorrese, Anna Fusco, Laura Vitiello, Stefania Amorosi, et al.. FOXN1 mutation abrogates prenatal T-cell development in humans. Journal of Medical Genetics, 2011, 48 (6), pp.413. ⟨10.1136/jmg.2011.089532⟩. ⟨hal-00624506⟩