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

• Published in: Immunity (Cambridge, Mass.) Vol. 42; no. 2; pp. 294 - 308
• Main Authors: Endo, Yusuke, Hirahara, Kiyoshi, Iinuma, Tomohisa, Shinoda, Kenta, Tumes, Damon J, Asou, Hikari K, Matsugae, Nao, Obata-Ninomiya, Kazushige, Yamamoto, Heizaburo, Motohashi, Shinichiro, Oboki, Keisuke, Nakae, Susumu, Saito, Hirohisa, Okamoto, Yoshitaka, Nakayama, Toshinori
• Format: Journal Article
• Language: English
• Published: United States Elsevier Limited 17.02.2015
• Subjects: Airway management; Animals; Asthma; Asthma - immunology; Asthma - pathology; Cells, Cultured; Gene expression; Humans; Immune system; Immunologic Memory - immunology; Inflammation - immunology; Inflammatory diseases; Interleukin-1 Receptor-Like 1 Protein; Interleukin-33; Interleukin-5 - biosynthesis; Interleukin-5 - immunology; Interleukins - genetics; Interleukins - immunology; Kinases; Lymphocytes; Medical research; Metabolic disorders; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Nasal Polyps - immunology; p38 Mitogen-Activated Protein Kinases - genetics; p38 Mitogen-Activated Protein Kinases - immunology; Pulmonary Eosinophilia - immunology; Receptors, Antigen, T-Cell - immunology; Receptors, Interleukin - genetics; Receptors, Interleukin - immunology; RNA Interference; RNA, Small Interfering; Science; Sinusitis - immunology; Studies; Th2 Cells - immunology
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2015.01.016

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.