The gene encoding early growth response 2, a target of the transcription factor NFAT, is required for the development and maturation of natural killer T cells.
The influence of signals transmitted by the phosphatase calcineurin and the transcription factor NFAT on the development and function of natural killer T (NKT) cells is unclear. In this report, we demonstrate that the transcription factor early growth response 2 (Egr2), a target gene of NFAT, was specifically required for the ontogeny of NKT cells but not that of conventional CD4(+) or CD8(+) T cells. NKT cells developed normally in the absence of Egr1 or Egr3, which suggests that Egr2 is a specific regulator of NKT cell differentiation. We found that Egr2 was important in the selection, survival and maturation of NKT cells. Our findings emphasize the importance of the calcineurin-NFAT-Egr2 pathway in the development of the NKT lymphocyte lineage.
Lazarevic
Vanja
V
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Zullo
Alfred J
AJ
Schweitzer
Michelle N
MN
Staton
Tracy L
TL
Gallo
Elena M
EM
Crabtree
Gerald R
GR
Glimcher
Laurie H
LH
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019703:Calcineurin / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D051767:Early Growth Response Protein 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050778:NFATC Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D055611:Natural Killer T-Cells / Q000276:immunology*
D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D050778:NFATC Transcription Factors; D019703:Calcineurin