Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33

• Published in: Blood 2009-02, Vol.113 (7), p.1526-1534
• Main Authors: Pecaric-Petkovic, Tatjana, Didichenko, Svetlana A., Kaempfer, Sacha, Spiegl, Nicole, Dahinden, Clemens A.
• Format: Article
• Language: English
• Subjects: Basophils - cytology; Basophils - immunology; Biological and medical sciences; CD28 Antigens - metabolism; CD3 Complex - metabolism; Cell Communication - immunology; Cell Membrane - metabolism; Cells, Cultured; Complement C5a - metabolism; Eosinophils - cytology; Eosinophils - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Hypersensitivity - immunology; Hypersensitivity - metabolism; Hypersensitivity - pathology; Immunobiology; Interleukin-1 - metabolism; Interleukin-1 Receptor-Like 1 Protein; Interleukin-13 - metabolism; Interleukin-18 - metabolism; Interleukin-3 - metabolism; Interleukin-33; Interleukin-4 - metabolism; Interleukin-8 - metabolism; Interleukins - immunology; Interleukins - metabolism; Leukotriene C4 - metabolism; Myeloid cells: ontogeny, maturation, markers, receptors; Neutrophils - cytology; Neutrophils - immunology; Phagocytes, Granulocytes, and Myelopoiesis; Polynuclears; Receptors, Cell Surface - metabolism; Signal Transduction - immunology; Solubility; Th2 Cells - cytology; Th2 Cells - immunology; Th2 Cells - metabolism
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2008-05-157818

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 FcϵRI-activation, and enhances FcϵRI-induced mediator release. These effects are similar to that of IL-3, but the signaling pathways engaged are distinct because IL-33 strongly activates NF-κB 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.