Submitted May 11, 2006
Accepted August 14, 2006
Human Langerhans cell activation triggered in vitro by conditionally expressed MKK6 is counter-regulated by the downstream effector RelB
Almut Jorgl, Barbara Platzer, Sabine Taschner, Leonhard X. Heinz, Bernhard Hocher, Peter M. Reisner, Florian Gobel, and Herbert Strobl*
Institute of Immunology, Medical University Vienna
Department of Biochemistry, University of Lausanne
* Corresponding author; email: herbert.strobl{at}meduniwien.ac.at.
Environmentally exposed epithelial Langerhans cells (LCs) encounter diverse innate stress signals, which lead to the activation of complex intracellular signaling cascades. Among these, p38 MAPK is consistently phosphorylated. For which aspects of LC activation triggering of p38 signaling is sufficient remains to be elucidated. We show that conditional induction of a dominant active form of MAPK kinase 6 (d.a.MKK6), a direct upstream kinase of p38, in LCs efficiently induces the upregulation of co-stimulatory molecules and enhances their T cell stimulatory capacity. These immediate effects showed no or only a minor requirement for classical NF-
B signaling. Concomitant with LC activation, d.a.MKK6 induced the alternative NF-B member RelB, whose nuclear localization marks mature DCs. Specific inhibition of nuclear RelB during d.a.MKK6-induced LC activation further enhanced their maturation state. This observation was validated using the p38 activator anisomycin thus suggesting a novel LC intrinsic control mechanism regulated by RelB.
