A role for Ly108 in the induction of promyelocytic zinc finger transcription factor in developing thymocytes.
The promyelocytic zinc finger transcription factor (PLZF) is required for the development of activated phenotypes in NKT and other innate T lymphocytes. Although strong TCR stimulation has been implicated in the induction of PLZF, the factors regulating PLZF expression are incompletely understood. We show in this study that costimulation of preselection double-positive thymocytes through the signaling lymphocyte activation molecule family receptor Ly108 markedly enhanced PLZF expression compared with that induced by TCR stimulation alone. Costimulation with Ly108 increased expression of early growth response protein (Egr)-2 and binding of Egr-2 to the promoter of Zbtb16, which encodes PLZF, and resulted in PLZF levels similar to those seen in NKT cells. In contrast, costimulation with anti-CD28 failed to enhance Egr-2 binding and Zbtb16 expression. Moreover, mice lacking Ly108 showed decreased numbers of PLZF-expressing CD4(+) T cells. Together, these results support a potential role for Ly108 in the induction of PLZF.
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Mala
M
Dutta
Zachary J
ZJ
Kraus
Julio
J
Gomez-Rodriguez
Sun-Hee
SH
Hwang
Jennifer L
JL
Cannons
Jun
J
Cheng
Sang-Yun
SY
Lee
David L
DL
Wiest
Edward K
EK
Wakeland
Pamela L
PL
Schwartzberg
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000950:Antigens, Ly / Q000235:genetics* / Q000276:immunology; D018106:CD28 Antigens / Q000037:antagonists & inhibitors / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D051767:Early Growth Response Protein 2 / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D060168:Thymocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D000071176:Signaling Lymphocytic Activation Molecule Family
D000906:Antibodies; D000950:Antigens, Ly; D018106:CD28 Antigens; D002118:Calcium; D051767:Early Growth Response Protein 2; D051741:Kruppel-Like Transcription Factors; D008070:Lipopolysaccharides; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D011948:Receptors, Antigen, T-Cell; C497327:Egr2 protein, mouse; C513267:Zbtb16 protein, mouse; C000604063:Slamf6 protein, mouse; D000071176:Signaling Lymphocytic Activation Molecule Family