The Interleukin-33-p38 Kinase Axis Confers Memory T Helper 2 Cell Pathogenicity in the Airway

被引：214

作者：

Endo, Yusuke ^{[1
]}

Hirahara, Kiyoshi ^{[2
]}

Iinuma, Tomohisa ^{[3
]}

Shinoda, Kenta ^{[1
]}

Tumes, Damon J. ^{[1
]}

Asou, Hikari K. ^{[1
]}

Matsugae, Nao ^{[1
]}

Obata-Ninomiya, Kazushige ^{[1
]}

Yamamoto, Heizaburo ^{[2
,3
]}

Motohashi, Shinichiro ^{[4
]}

Oboki, Keisuke ^{[6
]}

Nakae, Susumu ^{[5
]}

Saito, Hirohisa ^{[6
]}

Okamoto, Yoshitaka ^{[3
]}

Nakayama, Toshinori ^{[1
,7
]}

机构：

[1] Chiba Univ, Grad Sch Med, Dept Immunol, Chuo Ku, Chiba 2608670, Japan

[2] Chiba Univ, Grad Sch Med, Dept Adv Allergol Airway, Chuo Ku, Chiba 2608670, Japan

[3] Chiba Univ, Grad Sch Med, Dept Otorhinolaryngol, Chuo Ku, Chiba 2608670, Japan

[4] Chiba Univ, Grad Sch Med, Dept Med Immunol, Chuo Ku, Chiba 2608670, Japan

[5] Univ Tokyo, Ctr Expt Med & Syst Biol, Lab Syst Biol, Inst Med Sci,Minato Ku, Tokyo 1088639, Japan

[6] Natl Res Inst Child Hlth & Dev, Dept Allergy & Immunol, Setagaya Ku, Tokyo 1578535, Japan

[7] Japan Sci & Technol Agcy, CREST, Chuo Ku, Chiba 2608670, Japan

来源：

IMMUNITY | 2015年 / 42卷 / 02期

关键词：

INNATE LYMPHOID-CELLS; T-CELLS; FAMILY-MEMBERS; TH2; IL-33; ASTHMA; CYTOKINE; P38; TRANSCRIPTION; INFLAMMATION;

D O I：

10.1016/j.immuni.2015.01.016

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

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 immunerelated 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-33ST2-p38 signaling appears to directly instruct pathogenic memory Th2 cells to produce IL-5 and induce eosinophilic inflammation.

引用

页码：294 / 308

页数：15

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