Monocyte Surface-Bound IL-15 Can Function as an Activating Receptor and Participate in Reverse Signaling

Graham G. Neely, Slava Epelman, Ling Ling Ma, Pina Colarusso, Christopher J. Howlett, Ernest K. Amankwah, Amanda C. McIntyre, Stephen M. Robbins, Christopher H. Mody

Research output: Contribution to journalArticlepeer-review

Abstract

IL-15 is a short chain, four-α 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.

Original languageEnglish (US)
Pages (from-to)4225-4234
Number of pages10
JournalJournal of Immunology
Volume172
Issue number7
DOIs
StatePublished - Apr 1 2004
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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