Cytokine receptor-mediated trafficking of preformed IL-4 in eosinophils identifies an innate immune mechanism of cytokine secretion.
Although leukocytes of the innate immune system, including eosinophils, contain within their granules preformed stores of cytokines available for selective and rapid release, little is known about the mechanisms governing the mobilization and secretion of these cytokines. Here we show that a cytokine receptor, the IL-4 receptor alpha chain, mediates eotaxin-stimulated mobilization of preformed IL-4 from eosinophil granules into secretory vesicles. Eosinophils contain substantial intracellular quantities of several granule- and vesicle-associated cytokine receptors, including IL-4, IL-6, and IL-13 receptors as well as CCR3. Both IL-4 and IL-4 receptor alpha chain colocalized in eosinophil granules; and after eotaxin-stimulation, IL-4 receptor alpha chain, bearing bound IL-4, was mobilized into secretory vesicles. These findings indicate that intracellular cytokine receptors within secretory vesicles transport their cognate cytokines requisite for the secretion of cytokines preformed in innate immune leukocytes.
Departments of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Lisa A
LA
Spencer
Rossana C N
RC
Melo
Sandra A C
SA
Perez
Staci P
SP
Bafford
Ann M
AM
Dvorak
Peter F
PF
Weller
D002478:Cells, Cultured; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology* / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D011485:Protein Binding; D021381:Protein Transport; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000276:immunology; D018121:Receptors, Cytokine / Q000276:immunology*; D019948:Receptors, Interleukin-4 / Q000276:immunology; D019947:Receptors, Interleukin-6 / Q000378:metabolism
C515456:CCL11 protein, human; C515350:CCR3 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D019948:Receptors, Interleukin-4; D019947:Receptors, Interleukin-6; D015847:Interleukin-4