A domain of Foxn1 required for crosstalk-dependent thymic epithelial cell differentiation

Dong Ming Su, Samuel Navarre, Won Jong Oh, Brian G. Condie, Nancy R. Manley

Research output: Contribution to journalArticle

120 Scopus citations

Abstract

Thymic epithelial cells (TECs) are required for T cell maturation within the thymus. In the nude (Foxn1nu/nu) mouse, TECs fail to differentiate. We have generated a hypomorphic allele called Foxn1Δ, from which an N-terminal domain was deleted. The phenotype was thymus specific, identifying a tissue-specific activity for this domain. Foxn1Δ/Δ mice showed abnormal thymic architecture, lacking cortical and medullary domains. In contrast to thymi in mice with the null allele, the Foxn1Δ/Δ thymus promoted T cell development, but with specific defects at both the double-negative and double-positive stages. Thus, initiation and progression of TEC differentiation are genetically separable functions of Foxn1, and the N-terminal domain is required for crosstalk-dependent TEC differentiation.

Original languageEnglish
Pages (from-to)1128-1135
Number of pages8
JournalNature Immunology
Volume4
Issue number11
DOIs
StatePublished - 1 Nov 2003

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