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

Pecaric-Petkovic, Tatjana; Didichenko, Svetlana A; Kaempfer, Sacha; Spiegl, Nicole; Dahinden, Clemens A (2009). Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33. Blood, 113(7), pp. 1526-34. Washington, D.C.: American Society of Hematology 10.1182/blood-2008-05-157818

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute for Immunology (discontinued)

UniBE Contributor:

Dahinden, Clemens A.

ISSN:

0006-4971

ISBN:

18955562

Publisher:

American Society of Hematology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:04

Last Modified:

04 May 2014 23:20

Publisher DOI:

10.1182/blood-2008-05-157818

PubMed ID:

18955562

Web of Science ID:

000263316400019

URI:

https://boris.unibe.ch/id/eprint/27948 (FactScience: 114323)

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