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

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.

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Figure 1: Generation and characterization of the Foxn1Δ allele.
Figure 2: Thymocyte development markers in the Foxn1Δ/Δ adult thymus.
Figure 3: Epithelial cell phenotype in the adult thymus.
Figure 4: Epithelial cell phenotype in the fetal thymus.
Figure 5: CD4 and CD8 expression on fetal thymocytes.
Figure 6: CD44 and CD25 expression on triple-negative thymocytes.
Figure 7: Injection of TCRhi single-positive cells does not induce cortical and medullary formation.

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Acknowledgements

We thank L. Cheng and L. Swart for technical assistance. We thank E. Richie for advice and for reading the manuscript. Embryonic stem cell culture and chimera generation was done by the Medical College of Georgia Transgenic Core Facility. Cell sorting by MoFlo was done by the University of Georgia Flow Cytometry Core Facility. Supported by grants from the National Institutes of Health, Institute of Child Health and Human Development (HD035920) and the Institute of Allergy and Infectious Diseases (AI055001) to N.R.M.

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Correspondence to Nancy R Manley.

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Su, Dm., Navarre, S., Oh, Wj. et al. A domain of Foxn1 required for crosstalk-dependent thymic epithelial cell differentiation. Nat Immunol 4, 1128–1135 (2003). https://doi.org/10.1038/ni983

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