Monocyte surface-bound IL-15 can function as an activating receptor and participate in reverse signaling.
IL-15 is a short chain, four-alpha helix cytokine that shares some biological function with IL-2. One striking difference between IL-2 and IL-15 is the ability of monocytes to express IL-15 on their cell surface after activation. In the current study we have investigated the ability of human monocyte cell surface IL-15 to participate in reverse signaling. Cross-linking anti-IL-15 Abs were used as a surrogate ligand for surface IL-15 engagement. Ligation of cell surface-expressed IL-15 induced monocyte adhesion that required the activity of small m.w. GTPases. Reverse signals through surface IL-15 activated the Rho-GTPase Rac3. In addition, engagement of cell surface IL-15 was found to activate a number of signaling pathways, including both extracellular signal-regulated kinase 1/2 and p38, and resulted in the secretion of IL-8. IL-8 production required mitogen-activated protein kinase activity. Thus, the current study has established that cell surface IL-15 is more than just a ligand; it can function as a receptor and participate in reverse signaling that results in cellular adhesion and production of inflammatory cytokines.
Neely
Graham G
GG
Department of Medical Sciences, University of Calgary, Calgary, Alberta, Canada.
Epelman
Slava
S
Ma
Ling Ling
LL
Colarusso
Pina
P
Howlett
Christopher J
CJ
Amankwah
Ernest K
EK
McIntyre
Amanda C
AC
Robbins
Stephen M
SM
Mody
Christopher H
CH
D000328:Adult; D002448:Cell Adhesion / Q000276:immunology; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents / Q000378:metabolism; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000378:metabolism; D019409:Interleukin-15 / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D016209:Interleukin-8 / Q000096:biosynthesis; D020935:MAP Kinase Signaling System / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D009000:Monocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D012995:Solubility; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000502:physiology
D003432:Cross-Linking Reagents; D007106:Immune Sera; D019409:Interleukin-15; D016209:Interleukin-8; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D019010:Vascular Cell Adhesion Molecule-1; D020741:rho GTP-Binding Proteins