Development of promyelocytic zinc finger and ThPOK-expressing innate gamma delta T cells is controlled by strength of TCR signaling and Id3.
The broad-complex tramtrack and bric a brac-zinc finger transcriptional regulator (BTB-ZF), promyelocytic leukemia zinc finger (PLZF), was recently shown to control the development of the characteristic innate T cell phenotype and effector functions of NK T cells. Interestingly, the ectopic expression of PLZF was shown to push conventional T cells into an activated state that seems to be proinflammatory. The factors that control the normal expression of PLZF in lymphocytes are unknown. In this study, we show that PLZF expression is not restricted to NK T cells but is also expressed by a subset of gammadelta T cells, functionally defining distinct subsets of this innate T cell population. A second BTB-ZF gene, ThPOK, is important for the phenotype of the PLZF-expressing gammadelta T cells. Most importantly, TCR signal strength and expression of inhibitor of differentiation gene 3 control the frequency of PLZF-expressing gammadelta T cells. This study defines the factors that control the propensity of the immune system to produce potentially disease-causing T cell subsets.
Alonzo
Eric S
ES
Immunology Program, Sloan-Kettering Institute, New York, NY, 10065, USA.
Gottschalk
Rachel A
RA
Das
Joy
J
Egawa
Takeshi
T
Hobbs
Robin M
RM
Pandolfi
Pier Paolo
PP
Pereira
Pablo
P
Nichols
Kim E
KE
Koretzky
Gary A
GA
Jordan
Martha S
MS
Sant'Angelo
Derek B
DB
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics; D016130:Immunophenotyping; D051796:Inhibitor of Differentiation Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D016335:Zinc Fingers / Q000235:genetics / Q000276:immunology*
D051796:Inhibitor of Differentiation Proteins; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014157:Transcription Factors; C497211:Zbtb7b protein, mouse; C513267:Zbtb16 protein, mouse; C067679:Idb3 protein, mouse