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

Yusuke Endo, Kiyoshi Hirahara, Tomohisa Iinuma, Kenta Shinoda, Damon J. Tumes, Hikari K. Asou, Nao Matsugae, Kazushige Obata-Ninomiya, Heizaburo Yamamoto, Shinichiro Motohashi, Keisuke Oboki, Susumu Nakae, Hirohisa Saito, Yoshitaka Okamoto, Toshinori Nakayama

Research output: Contribution to journalArticlepeer-review

188 Citations (Scopus)


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+ Tcells 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.

Original languageEnglish
Pages (from-to)294-308
Number of pages15
Issue number2
Publication statusPublished or Issued - 17 Feb 2015
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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