TY - JOUR
T1 - Mature T cells depend on signaling through the IKK complex
AU - Schmidt-Supprian, Marc
AU - Courtois, Gilles
AU - Tian, Jane
AU - Coyle, Anthony J.
AU - Israël, Alain
AU - Rajewsky, Klaus
AU - Pasparakis, Manolis
N1 - Funding Information:
We are grateful to C. Göttlinger and N. Bartenev for cell sorting; to A. Egert, C. Chable-Bessia, V. Dreier, B. Hampel, A. Roth, and C. Uthoff-Hachenberg for technical help; to V. Heissmeier and C. Schmidt for advice; and to I. Aifantis, C. Kanellopoulou, and Y. Sasaki for critical reading of the manuscript. We thank J. Marth and C.B. Wilson for Cre-transgenic mice. This work was supported by a grant from Ligue Nationale contre le Cancer (Equipe Labelisée) and from Association pour la Recherche sur le Cancer to A.I., by a grant from the Cologne Centre for Molecular Medicine (ZMMK) to W. Muller and K.R., and by grants from the Körber Foundation, the European Union (QLG1-CT-1999-00202), and the Deutsche Forschungsgemeinschaft (SFB 243) to K.R. M.P. received fellowship awards from the European Molecular Biology Organization and from the Leukemia and Lymphoma Society.
PY - 2003/9/1
Y1 - 2003/9/1
N2 - The transcription factor NF-κB is implicated in various aspects of T cell development and function. The IκB kinase (IKK) complex, consisting of two kinases, IKK1/α and IKK2/β, and the NEMO/IKKγ regulatory subunit, mediates NF-κB activation by most known stimuli. Adoptive transfer experiments had demonstrated that IKK1 and IKK2 are dispensable for T cell development. We show here that T lineage-specific deletion of IKK2 allows survival of naive peripheral T cells but interferes with the generation of regulatory and memory T cells. T cell-specific ablation of NEMO or replacement of IKK2 with a kinase-dead mutant prevent development of peripheral T cells altogether. Thus, IKK-induced NF-κB activation, mediated by either IKK1 or IKK2, is essential for the generation and survival of mature T cells, and IKK2 has an additional role in regulatory and memory T cell development.
AB - The transcription factor NF-κB is implicated in various aspects of T cell development and function. The IκB kinase (IKK) complex, consisting of two kinases, IKK1/α and IKK2/β, and the NEMO/IKKγ regulatory subunit, mediates NF-κB activation by most known stimuli. Adoptive transfer experiments had demonstrated that IKK1 and IKK2 are dispensable for T cell development. We show here that T lineage-specific deletion of IKK2 allows survival of naive peripheral T cells but interferes with the generation of regulatory and memory T cells. T cell-specific ablation of NEMO or replacement of IKK2 with a kinase-dead mutant prevent development of peripheral T cells altogether. Thus, IKK-induced NF-κB activation, mediated by either IKK1 or IKK2, is essential for the generation and survival of mature T cells, and IKK2 has an additional role in regulatory and memory T cell development.
UR - https://www.scopus.com/pages/publications/0141678951
U2 - 10.1016/S1074-7613(03)00237-1
DO - 10.1016/S1074-7613(03)00237-1
M3 - Article
C2 - 14499113
AN - SCOPUS:0141678951
SN - 1074-7613
VL - 19
SP - 377
EP - 389
JO - Immunity
JF - Immunity
IS - 3
ER -
SDG 3 Good Health and Well-being