Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-58766
Hofmann, J; Mair, F; Greter, M; Schmidt-Supprian, M; Becher, B (2011). NIK signaling in dendritic cells but not in T cells is required for the development of effector T cells and cell-mediated immune responses. Journal of Experimental Medicine, 208(9):1917-1929.
View at publisher
The canonical NF-κB pathway is a driving force for virtually all aspects of inflammation. Conversely, the role of the noncanonical NF-κB pathway and its central mediator NF-κB-inducing kinase (NIK) remains poorly defined. NIK has been proposed to be involved in the formation of T(H)17 cells, and its absence in T(H) cells renders them incapable of inducing autoimmune responses, suggesting a T cell-intrinsic role for NIK. Upon systematic analysis of NIK function in cell-mediated immunity, we found that NIK signaling is dispensable within CD4(+) T cells but played a pivotal role in dendritic cells (DCs). We discovered that NIK signaling is required in DCs to deliver co-stimulatory signals to CD4(+) T cells and that DC-restricted expression of NIK is sufficient to restore T(H)1 and T(H)17 responses as well as cell-mediated immunity in NIK(-/-) mice. When CD4(+) T cells developed in the absence of NIK-sufficient DCs, they were rendered anergic. Reintroduction of NIK into DCs allowed developing NIK(-/-) CD4(+) T cells to become functional effector populations and restored the development of autoimmune disease. Therefore, our data suggest that a population of thymic DCs requires NIK to shape the formation of most αβ CD4(+) T effector lineages during early development.
0 downloads since deposited on 27 Feb 2012
33 downloads since 12 months
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Institute of Experimental Immunology|
|Dewey Decimal Classification:||570 Life sciences; biology
610 Medicine & health
|Deposited On:||27 Feb 2012 20:36|
|Last Modified:||30 Nov 2013 01:45|
|Publisher:||Rockefeller University Press|
Users (please log in): suggest update or correction for this item
Repository Staff Only: item control page