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

Abstract

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 FcepsilonRI-activation, and enhances FcepsilonRI-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-kappaB 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.

• Authors: Tatjana Pecaric-Petkovic, Svetlana A Didichenko, Sacha Kaempfer, Nicole Spiegl, Clemens A Dahinden
• Journal: Blood (Blood) Vol. 113 Issue 7 Pg. 1526-34 (Feb 12 2009) ISSN: 1528-0020 [Electronic] United States
• PMID: 18955562 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD28 Antigens
• CD3 Complex
• IL1RL1 protein, human
• IL33 protein, human
• IL4 protein, human
• Interleukin-1
• Interleukin-1 Receptor-Like 1 Protein
• Interleukin-13
• Interleukin-18
• Interleukin-3
• Interleukin-33
• Interleukin-8
• Interleukins
• Receptors, Cell Surface
• Interleukin-4
• Leukotriene C4
• Complement C5a

Topics

• Basophils (cytology, immunology)
• CD28 Antigens (metabolism)
• CD3 Complex (metabolism)
• Cell Communication (immunology)
• Cell Membrane (metabolism)
• Cells, Cultured
• Complement C5a (metabolism)
• Eosinophils (cytology, immunology)
• Humans
• Hypersensitivity (immunology, metabolism, pathology)
• 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, metabolism)
• Leukotriene C4 (metabolism)
• Neutrophils (cytology, immunology)
• Receptors, Cell Surface (metabolism)
• Signal Transduction (immunology)
• Solubility
• Th2 Cells (cytology, immunology, metabolism)