Receptors and Cytokine Transport

Science's STKE  07 Mar 2006:
Vol. 2006, Issue 325, pp. tw81
DOI: 10.1126/stke.3252006tw81

Eosinophils are leukocytes that participate in innate immune responses, the body's first line of defense against infection. These cells are on call, ready to secrete cytokines that enhance the immune response. These cytokines are stored in cytoplasmic granules. These granules store a mixture of cytokines, but eosinophils have a remarkable ability to secrete specific cytokines in response to a particular stimulus. Spencer et al. present evidence that the cells use inactive cytokine receptors to sort and mobilize particular cytokines to the cell surface for secretion. Eosinophils respond to the cytokine eotaxin (also called CCL11) by secreting interleukin-4 (IL-4), but not IL-12 or interferon-γ. Spencer et al. showed that IL-4 was present in cytoplasmic granules and found that a previously unrecognized pool of the IL-4 receptor protein IL-4Rα was also present in the granules. When cells were stimulated with eotaxin, immunoelectron microscopy showed that IL-4Rα, the ligand-binding subunit of the IL-4 receptor, moved along with IL-4 to vesicles that appeared to bud off of the cytoplasmic granules. The IL-4 receptor subunit known as γc, which is required for receptor signaling, was not transported with the IL-4Rα chain. Thus, eosinophils appear to use the cytokine-binding receptor subunit to selectively mobilize IL-4 while keeping the receptor subunits separated to avoid unwanted signaling through the receptor.

L. A. Spencer, R. C. N. Melo, S. A. C. Perez, S. P. Bafford, A. M. Dvorak, P. F. Weller, Cytokine receptor-mediated trafficking of preformed IL-4 in eosinophils identifies an innate immune mechanism of cytokine secretion. Proc. Natl. Acad. Sci. U.S.A. 103, 3333-3338 (2006). [Abstract] [Full Text]