Essential role of TAK1 in thymocyte development and activation.
The protein kinase TAK1 mediates the activation of NF-kappaB in response to stimulation by proinflammatory cytokines and microbial pathogens in the innate immunity pathways. However, the physiological function of TAK1 in the adaptive immunity pathways is unclear. By engineering mice lacking TAK1 in T cells, here, we show that TAK1 is essential for thymocyte development and activation in vivo. Deletion of TAK1 prevented the maturation of single-positive thymocytes displaying CD4 or CD8, leading to reduction of T cells in the peripheral tissues. Thymocytes lacking TAK1 failed to activate NF-kappaB and JNK and were prone to apoptosis upon stimulation. Our results provide the genetic evidence that TAK1 is required for the activation of NF-kappaB in thymocytes and suggest that TAK1 plays a central role in both innate and adaptive immunity.
Liu
Hong-Hsing
HH
Department of Molecular Biology and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
Xie
Min
M
Schneider
Michael D
MD
Chen
Zhijian J
ZJ
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D018390:Gene Targeting; D007109:Immunity / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology*; D000099151:MAP Kinase Kinase Kinase 7
D015704:CD4 Antigens; D016827:CD8 Antigens; D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D000099151:MAP Kinase Kinase Kinase 7