Article: article from journal or magazin.
Regulation of gammadelta versus alphabeta T lymphocyte differentiation by the transcription factor SOX13.
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't Publication Status: ppublish
alphabeta and gammadelta T cells originate from a common, multipotential precursor population in the thymus, but the molecular mechanisms regulating this lineage-fate decision are unknown. We have identified Sox13 as a gammadelta-specific gene in the immune system. Using Sox13 transgenic mice, we showed that this transcription factor promotes gammadelta T cell development while opposing alphabeta T cell differentiation. Conversely, mice deficient in Sox13 expression exhibited impaired development of gammadelta T cells but not alphabeta T cells. One mechanism of SOX13 function is the inhibition of signaling by the developmentally important Wnt/T cell factor (TCF) pathway. Our data thus reveal a dominant pathway regulating the developmental fate of these two lineages of T lymphocytes.
Animals, Antigens, CD4/genetics, Autoantigens/genetics, Autoantigens/metabolism, Cell Line, Cell Lineage, Cell Proliferation, Embryonic Development, Gene Expression Profiling, Gene Expression Regulation, Gene Rearrangement, T-Lymphocyte, High Mobility Group Proteins/genetics, High Mobility Group Proteins/metabolism, Humans, Lymphopoiesis, Mice, Mice, Transgenic, Receptors, Antigen, T-Cell, alpha-beta/analysis, Receptors, Antigen, T-Cell, gamma-delta/analysis, Receptors, Antigen, T-Cell, gamma-delta/genetics, Signal Transduction, T Cell Transcription Factor 1/physiology, T-Lymphocyte Subsets/cytology, T-Lymphocyte Subsets/immunology, Wnt Proteins/metabolism
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