Foxp1 is an essential transcriptional regulator for the generation of quiescent naive T cells during thymocyte development

Author:

Feng Xiaoming1,Ippolito Gregory C.2,Tian Lifeng1,Wiehagen Karla1,Oh Soyoung1,Sambandam Arivazhagan3,Willen Jessica1,Bunte Ralph M.4,Maika Shanna D.2,Harriss June V.2,Caton Andrew J.1,Bhandoola Avinash3,Tucker Philip W.2,Hu Hui1

Affiliation:

1. Immunology Program and Wistar Vaccine Center, The Wistar Institute, Philadelphia, PA;

2. Department of Molecular Genetics and The Institute for Cellular and Molecular Biology, The University of Texas at Austin; and

3. Department of Pathology and Laboratory Medicine and

4. University Laboratory Animal Resources, University of Pennsylvania, Philadelphia

Abstract

Abstract Proper thymocyte development is required to establish T-cell central tolerance and to generate naive T cells, both of which are essential for T-cell homeostasis and a functional immune system. Here we demonstrate that the loss of transcription factor Foxp1 results in the abnormal development of T cells. Instead of generating naive T cells, Foxp1-deficient single-positive thymocytes acquire an activated phenotype prematurely in the thymus and lead to the generation of peripheral CD4+ T and CD8+ T cells that exhibit an activated phenotype and increased apoptosis and readily produce cytokines upon T-cell receptor engagement. These results identify Foxp1 as an essential transcriptional regulator for thymocyte development and the generation of quiescent naive T cells.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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