Alternatively activated macrophages express the IL-27 receptor alpha chain WSX-1.
The interleukin (IL)-27 receptor-alpha WSX-1 is one component of the heterodimeric IL-27 receptor that is expressed on various cell types including macrophages. We previously demonstrated that IL-27 induces STAT-3 and is able to inhibit the production of pro-inflammatory cytokines in activated macrophages suggesting a novel feed-back mechanism by which IL-27 can modulate excessive inflammation. Because IL-4 receptor-alpha (IL-4Ralpha)-induced alternatively activated macrophages have also been described to attenuate pathological inflammatory immune responses, we analyzed the contribution of IL-27 in alternative macrophage activation. In the present study, like IL-10 and IL-4, IL-27 was found to suppress IL-12/23p40 production in activated bone marrow-derived macrophages. Whereas IL-10 induced the upregulation of the IL-4Ralpha on macrophages, receptor expression was not triggered by IL-27. In contrast to IL-4, IL-27 did not induce alternative macrophage activation but IL-4 strongly upregulated the expression of WSX-1 on macrophages and alternative macrophage activation enhanced IL-27-mediated signalling. We therefore conclude from our study that IL-10, IL-4 and IL-27 collaborate in modulating macrophage activation by successive upregulation of the IL-4Ralpha and WSX-1 on alternatively activated macrophages.
Rückerl
Dominik
D
Junior Research Group Molecular Infection Biology, Research Center Borstel, Parkallee 22, D-23845 Borstel, Germany. drueckerl@fz-borstel.de
Hessmann
Manuela
M
Yoshimoto
Takayuki
T
Ehlers
Stefan
S
Hölscher
Christoph
C
D000818:Animals; D002478:Cells, Cultured; D016753:Interleukin-10 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D007378:Interleukins / Q000502:physiology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018121:Receptors, Cytokine / Q000235:genetics*; D018123:Receptors, Interleukin
C486767:Il27 protein, mouse; C484747:Il27ra protein, mouse; D007378:Interleukins; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D016753:Interleukin-10; D015847:Interleukin-4