A role for IL-27p28 as an antagonist of gp130-mediated signaling.
The heterodimeric cytokine interleukin 27 (IL-27) signals through the IL-27Rα subunit of its receptor, combined with gp130, a common receptor chain used by several cytokines, including IL-6. Notably, the IL-27 subunits p28 (IL-27p28) and EBI3 are not always expressed together, which suggests that they may have unique functions. Here we show that IL-27p28, independently of EBI3, antagonized cytokine signaling through gp130 and IL-6-mediated production of IL-17 and IL-10. Similarly, the ability to generate antibody responses was dependent on the activity of gp130-signaling cytokines. Mice transgenic for expression of IL-27p28 showed a substantial defect in the formation of germinal centers and antibody production. Thus, IL-27p28, as a natural antagonist of gp130-mediated signaling, may be useful as a therapeutic for managing inflammation mediated by cytokines that signal through gp130.
University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA.
Jason S
JS
Stumhofer
Elia D
ED
Tait
William J
WJ
Quinn
Nancy
N
Hosken
Björn
B
Spudy
Radhika
R
Goenka
Ceri A
CA
Fielding
Aisling C
AC
O'Hara
Yi
Y
Chen
Michael L
ML
Jones
Christiaan J M
CJ
Saris
Stefan
S
Rose-John
Daniel J
DJ
Cua
Simon A
SA
Jones
Merle M
MM
Elloso
Joachim
J
Grötzinger
Michael P
MP
Cancro
Steven D
SD
Levin
Christopher A
CA
Hunter
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002469:Cell Separation; D050822:Cytokine Receptor gp130 / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007378:Interleukins / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015778:Minor Histocompatibility Antigens; D018121:Receptors, Cytokine / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*
D016207:Cytokines; C499601:Ebi3 protein, mouse; C486767:Il27 protein, mouse; C494200:Il6st protein, mouse; D007378:Interleukins; D015778:Minor Histocompatibility Antigens; D018121:Receptors, Cytokine; D050822:Cytokine Receptor gp130