Regulation of gammadelta versus alphabeta T lymphocyte differentiation by the transcription factor SOX13.
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.
Melichar
Heather J
HJ
Department of Pathology, Graduate Program in Immunology and Virology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Narayan
Kavitha
K
Der
Sandy D
SD
Hiraoka
Yoshiki
Y
Gardiol
Noemie
N
Jeannet
Gregoire
G
Held
Werner
W
Chambers
Cynthia A
CA
Kang
Joonsoo
J
D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D015704:CD4 Antigens / Q000235:genetics; D002460:Cell Line; D019070:Cell Lineage; D049109:Cell Proliferation; D047108:Embryonic Development; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015329:Gene Rearrangement, T-Lymphocyte; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D038041:Lymphopoiesis; D051379:Mice; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis* / Q000235:genetics; D015398:Signal Transduction; D051822:T Cell Transcription Factor 1 / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism
D001324:Autoantigens; D015704:CD4 Antigens; D006609:High Mobility Group Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; C110455:Sox13 protein, mouse; D051822:T Cell Transcription Factor 1; D051153:Wnt Proteins