An alternative pathway of NF-kappaB activation results in maturation and T cell priming activity of dendritic cells overexpressing a mutated IkappaBalpha - PubMed (original) (raw)

. 2007 Feb 1;178(3):1301-11.

doi: 10.4049/jimmunol.178.3.1301.

Sofia Buonocore, Ezra Aksoy, Najate Ouled-Haddou, Stanislas Goriely, Elena Lazarova, Frédéric Paulart, Carlo Heirman, Elsy Vaeremans, Kris Thielemans, Michel Goldman, Véronique Flamand

Affiliations

An alternative pathway of NF-kappaB activation results in maturation and T cell priming activity of dendritic cells overexpressing a mutated IkappaBalpha

Fabrice Moore et al. J Immunol. 2007.

Abstract

Maturation of dendritic cells (DC) is a critical step in the induction of T cell responses and depends on the activation of NF-kappaB transcription factors. Therefore, inhibition of NF-kappaB activation has been proposed as a strategy to maintain DC in an immature stage and to promote immune tolerance. Herein, we generated murine myeloid DC expressing a mutated IkappaBalpha acting as a superrepressor of the classical NF-kappaB pathway (s-rIkappaB DC) to investigate the consequences of NF-kappaB inhibition on the ability of DC to prime T cell responses. Upon in vitro LPS activation, maturation of s-rIkappaB DC was profoundly impaired as indicated by defective up-regulation of MHC class II and costimulatory molecules and reduced secretion of IL-12 p70 and TNF-alpha. In contrast, after injection, s-rIkappaB DC had the same capacity as control DC to migrate to draining lymph node and to induce Th1- and Th2-type cytokine production in a MHC class II-incompatible host mice. Likewise, s-rIkappaB DC pulsed with OVA were as efficient as control DC to induce Ag-specific T cell responses in vivo. Indeed, further in vitro experiments established that s-rIkappaB DC undergo efficient maturation upon prolonged contact with activated T cells via the alternative pathway of NF-kappaB activation triggered at least partly by lymphotoxin beta receptor ligation and involving processing of p100/RelB complexes.

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