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-mediated apoptosis in fibroblasts by TRAF2 recruitment to the IL-15R chain
* Institute of Immunology,
¶ Department of Urology,
Department of Pathology, University Hospital Benjamin Franklin, Free University, Berlin, Germany;
§ Department of Dermatology, University Hospital Eppendorf, University of Hamburg, Germany; and
Department of Internal Medicine IV, Friedrich-Alexander-University, Erlangen, Germany
1Correspondence: Institute of Immunology, University Hospital Benjamin Franklin. Free University Berlin, Hindenburgdamm 30, D-12200 Berlin, Germany. E-mail: bulfone{at}zedat.fu-berlin.de
Interleukin-15 (IL-15) is a potent inhibitor of several apoptosis
pathways. One prominent path toward apoptosis is the ligand-induced
association of TNF receptor 1 (TNFR1) with death domain adaptor
proteins. Studying if and how IL-15 blocks TNFR1-mediated apoptosis in
a murine fibroblast cell line (L929), we show here that IL-15 blocks
TNFR1-induced apoptosis via IL-15R
chain signaling. The
intracellular tail of IL-15R shows sequence homologies to the TRAF2
binding motifs of CD30 and CD40. Most important, binding of IL-15 to
IL-15R successfully competes with the TNFR1 complex for TRAF2
binding, which may impede assembly of key adaptor proteins to the TNFR1
complex, and induces I
B phosphorylation. Thus, IL-15R chain
stimulation is a powerful deflector of cell death very early in the
apoptosis signaling cascade, while TNF- and IL-15 surface as major
opponents in apoptosis control.—Bulfone-Paus, S., Bulanova, E., Pohl,
T., Budagian, V., Dürkop, H., Rückert, R., Kunzendorf, U.,
Paus, R., Krause, H. Death deflected: IL-15 inhibits TNF--mediated
apoptosis in fibroblasts by TRAF2 recruitment to the IL-15R chain.
Key Words: cell death • TNFR1 • L929 • IB
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