The Foxn1-dependent transcripts PCOLCE2 and mPPP1R16B are not required for normal thymopoiesis.
The adaptive immune system relies on the thymic microenvironment for the production of a diverse, self-tolerant T cell receptor repertoire. The central cellular organizer of the thymic microenvironment is the thymic epithelial cell (TEC). The development of TEC from endodermal precursor cells is under the control of the forkhead/winged helix transcription factor Foxn1 but the transcriptional program that leads to this unique epithelial differentiation has not been investigated functionally. Here, we show that expression of procollagen C-proteinase enhancer 2 (PCOLCE2) is absent in Foxn1-deficient TEC. In order to study the functional role of this gene in TEC differentiation, we have genetically inactivated PCOLCE2 and the gene encoding phosphatase 1 regulatory inhibitory subunit 16B (mPPP1R16B), another transcript lacking in Foxn1-deficient TEC. Mice deficient for either one or both of these transcripts presented a normal thymic microenvironment and undisturbed thymopoiesis. While there is no evidence for a functional role of PCOLCE2 and mPPP1R16B in thymus development, our results suggest that the lack of thymopoiesis in Foxn1-deficient mice is caused by multiple functional defects.
The Max-Planck-Institute of Immunobiology, Department of Developmental Immunology, Freiburg, Germany.
Kornelia
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Heinzel
Conrad C
CC
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D000818:Animals; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*
D051858:Forkhead Transcription Factors; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C491552:Pcolce2 protein, mouse; C486763:Ppp1r16b protein, mouse; C090140:Whn protein