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Immunity. 2015 Feb 17;42(2):294-308. doi: 10.1016/j.immuni.2015.01.016.

The interleukin-33-p38 kinase axis confers memory T helper 2 cell pathogenicity in the airway.

Author information

1
Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
2
Department of Advanced Allergology of the Airway, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
3
Department of Otorhinolaryngology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
4
Department of Advanced Allergology of the Airway, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan; Department of Otorhinolaryngology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
5
Department of Medical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
6
Department of Allergy and Immunology, National Research Institute for Child Health and Development, 2-10-1 Okura Setagaya-ku, Tokyo 157-8535, Japan.
7
Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
8
Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan; CREST, Japan Science and Technology Agency, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan. Electronic address: tnakayama@faculty.chiba-u.jp.

Abstract

Memory CD4(+) T helper (Th) cells provide long-term protection against pathogens and are essential for the development of vaccines; however, some antigen-specific memory Th cells also drive immune-related pathology, including asthma. The mechanisms regulating the pathogenicity of memory Th cells remain poorly understood. We found that interleukin-33 (IL-33)-ST2 signals selectively licensed memory Th2 cells to induce allergic airway inflammation via production of IL-5 and that the p38 MAP kinase pathway was a central downstream target of IL-33-ST2 in memory Th2 cells. In addition, we found that IL-33 induced upregulation of IL-5 by memory CD4(+) T cells isolated from nasal polyps of patients with eosinophilic chronic rhinosinusitis. Thus, IL-33-ST2-p38 signaling appears to directly instruct pathogenic memory Th2 cells to produce IL-5 and induce eosinophilic inflammation.

PMID:
25692703
DOI:
10.1016/j.immuni.2015.01.016
[Indexed for MEDLINE]
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