IL-1β, IL-4 and IL-12 control the fate of group 2 innate lymphoid cells in human airway inflammation in the lungs

被引：398

作者：

Bal, Suzanne M. ^{[1
]}

Bernink, Jochem H. ^{[1
]}

Nagasawa, Maho ^{[1
]}

Groot, Jelle ^{[1
]}

Shikhagaie, Medya M. ^{[1
]}

Golebski, Kornel ^{[1
,2
]}

van Drunen, Cornelis M. ^{[2
]}

Lutter, Rene ^{[3
,4
]}

Jonkers, Rene E. ^{[4
]}

Hombrink, Pleun ^{[5
]}

Bruchard, Melanie ^{[1
]}

Villaudy, Julien ^{[6
]}

Munneke, J. Marius ^{[7
]}

Fokkens, Wytske ^{[2
]}

Erjefalt, Jonas S. ^{[8
]}

Spits, Hergen ^{[1
]}

Ros, Xavier Romero ^{[1
]}

机构：

[1] Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands

[2] Univ Amsterdam, Acad Med Ctr, Dept Otorhinolaryngol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands

[3] Univ Amsterdam, Acad Med Ctr, Dept Expt Immunol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands

[4] Univ Amsterdam, Acad Med Ctr, Dept Pulmonol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands

[5] Sanquin Res & Landsteiner Lab, Amsterdam, Netherlands

[6] Univ Amsterdam, Acad Med Ctr, Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands

[7] Univ Amsterdam, Acad Med Ctr, Dept Hematol, NL-1105 AZ Amsterdam, Netherlands

[8] Lund Univ, Dept Expt Med Sci, Unit Airway Inflammat, Lund, Sweden

来源：

NATURE IMMUNOLOGY | 2016年 / 17卷 / 06期

基金：

欧洲研究理事会;

关键词：

NASAL POLYPS; ASTHMA; EXPRESSION; DUPILUMAB; ADULTS;

D O I：

10.1038/ni.3444

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Group 2 innate lymphoid cells (ILC2s) secrete type 2 cytokines, which protect against parasites but can also contribute to a variety of inflammatory airway diseases. We report here that interleukin 1 beta (IL-1 beta) directly activated human ILC2s and that IL-12 induced the conversion of these activated ILC2s into interferon-gamma (IFN-gamma )-producing ILC1s, which was reversed by IL-4. The plasticity of ILCs was manifested in diseased tissues of patients with severe chronic obstructive pulmonary disease (COPD) or chronic rhinosinusitis with nasal polyps (CRSwNP), which displayed IL-12 or IL-4 signatures and the accumulation of ILC1s or ILC2s, respectively. Eosinophils were a major cellular source of IL-4, which revealed cross-talk between IL-5-producing ILC2s and IL-4-producing eosinophils. We propose that IL-12 and IL-4 govern ILC2 functional identity and that their imbalance results in the perpetuation of type 1 or type 2 inflammation.

引用

页码：636 / +

页数：12

共 46 条

[1] Innate Immune Defenses Mediated by Two ILC Subsets Are Critical for Protection against Acute Clostridium difficile Infection [J].