期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 205, 期 11, 页码 2595-2608出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20080452
关键词
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资金
- National Institute for Allergy and Infectious Diseases Intramural Program
- Finnish Cultural Foundation
- Finnish Medical Foundation
- Emil Aaltonen Foundation
Interleukin (IL)-4 and -13 are related cytokines sharing functional receptors. IL-4 signals through the type I (IL-4R alpha/common gamma-chain [gamma c]) and the type II (IL-4R alpha/-13R alpha 1) IL-4 receptors, whereas IL-13 utilizes only the type II receptor. In this study, we show that mouse bone marrow-derived macrophages and human and mouse monocytes showed a much greater sensitivity to IL-4 than to IL-13. Lack of functional gamma c made these cells poorly responsive to IL-4, while retaining full responsiveness to IL-13. In mouse peritoneal macrophages, IL-4 potency exceeds that of IL-13, but lack of gamma c had only a modest effect on IL-4 signaling. In contrast, IL-13 stimulated greater responses than IL-4 in fibroblasts. Using levels of receptor chain expression and known binding affinities, we modeled the assemblage of functional type I and II receptor complexes. The differential expression of IL-4R alpha, IL-13R alpha 1, and gamma c accounted for the distinct IL-4-IL-13 sensitivities of the various cell types. These findings provide an explanation for IL-13's principal function as an effector cytokine and IL-4's principal role as an immunoregulatory cytokine.
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