c-Rel but not NF-kappaB1 is important for T regulatory cell development.
Regulatory T (Treg) cells are crucial for maintaining peripheral tolerance and controlling T-cell responses. The generation of Treg in the thymus requires TCR triggering and CD28 costimulation. Engagement of these receptors induces a number of signalling pathways, including the activation of NF-kappaB via PKCtheta and the Bcl-10/CARMA1/MALT complex. Previous studies have shown that PKCtheta, Bcl-10 and CARMA1 are important for Treg development. It is unclear, however, whether different members of the NF-kappaB family contribute to Treg development or homeostasis. In this study, we show that Treg numbers are reduced in the absence of c-Rel but not NF-kappaB1 (p50). Furthermore, using mixed bone marrow chimeras from WT and KO animals, we demonstrate that the requirement for PKCtheta, Bcl-10 and c-Rel is T-cell intrinsic, and cannot be rescued by the presence of WT cells. Therefore, c-Rel and NF-kappaB1 have differential roles in Treg development.
Deenick
Elissa K
EK
Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Toronto, Ont., Canada.
Elford
Alisha R
AR
Pellegrini
Marc
M
Hall
Håkan
H
Mak
Tak W
TW
Ohashi
Pamela S
PS
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000276:immunology*; D020569:Proto-Oncogene Proteins c-rel / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology
D016328:NF-kappa B; D020569:Proto-Oncogene Proteins c-rel