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Blood, 12 February 2009, Vol. 113, No. 7, pp. 1526-1534. Prepublished online as a Blood First Edition Paper on October 27, 2008; DOI 10.1182/blood-2008-05-157818.
PHAGOCYTES, GRANULOCYTES, AND MYELOPOIESIS Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-331 Institute of Immunology, University Hospital Bern, Inselspital, Bern, Switzerland
In mice, interleukin-18 (IL-18) regulates Th1- or Th2-type immune responses depending on the cytokine environment and effector cells involved, and the ST2-ligand, IL-33, primarily promotes an allergic phenotype. Human basophils, major players in allergic inflammation, constitutively express IL-18 receptors, while ST2 surface expression is inducible by IL-3. Unexpectedly, freshly isolated basophils are strongly activated by IL-33, but, in contrast to mouse basophils, do not respond to IL-18. IL-33 promotes IL-4, IL-13 and IL-8 secretion in synergy with IL-3 and/or Fc
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| Copyright © 2009 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
RI-activation, and enhances Fc
B and shows a preference for p38 MAP-kinase, while IL-3 acts through Jak/Stat and preferentially activates ERK. Eosinophils are the only other leukocyte-type directly activated by IL-33, as evidenced by screening of p38-activation in peripheral blood cells. Only upon CD3/CD28-ligation, IL-33 weakly enhances Th2 cytokine expression by in vivo polarized Th2 cells. This study on primary human cells demonstrates that basophils and eosinophils are the only direct target leukocytes for IL-33, suggesting that IL-33 promotes allergic inflammation and Th2 polarization mainly by the selective activation of these specialized cells of the innate immune system. 
