PD-1 regulates KLRG1+ group 2 innate lymphoid cells

被引：165

作者：

Taylor, Samuel ^{[1
]}

Huang, Yuefeng ^{[2
]}

Mallett, Grace ^{[4
]}

Stathopoulou, Chaido ^{[4
]}

Felizardo, Tania C. ^{[1
]}

Sun, Ming-An ^{[3
]}

Martin, Evelyn L. ^{[4
]}

Zhu, Nathaniel ^{[1
]}

Woodward, Emma L. ^{[4
]}

Elias, Martina S. ^{[4
]}

Scott, Jonathan ^{[4
]}

Reynolds, Nick J. ^{[4
,5
]}

Paul, William E.

Fowler, Daniel H. ^{[1
]}

Amarnath, Shoba ^{[4
]}

机构：

[1] NCI, Expt Transplantat Immunol Branch, NIH, Bethesda, MD 20892 USA

[2] NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA

[3] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA

[4] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

[5] Royal Victoria Infirm, Dept Dermatol, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2017年 / 214卷 / 06期

基金：

英国工程与自然科学研究理事会; 美国国家卫生研究院;

关键词：

GASTRIC EPITHELIAL-CELLS; CHRONIC VIRAL-INFECTION; NATURAL HELPER-CELLS; T-CELLS; TYPE-2; IMMUNITY; AIRWAY HYPERREACTIVITY; ALLERGIC INFLAMMATION; LUNG INFLAMMATION; EXPRESSION; MICE;

D O I：

10.1084/jem.20161653

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 (ILC-2s) regulate immune responses to pathogens and maintain tissue homeostasis in response to cytokines. Positive regulation of ILC-2s through ICOS has been recently elucidated. We demonstrate here that PD-1 is an important negative regulator of KLRG1(+) ILC-2 function in both mice and humans. Increase in KLRG1(+) ILC-2 cell numbers was attributed to an intrinsic defect in PD-1 signaling, which resulted in enhanced STAT5 activation. During Nippostrongylus brasiliensis infection, a significant expansion of KLRG1(+) ILC-2 subsets occurred in Pdcd1(-/-) mice and, upon adoptive transfer, Pdcd1(-/-) KLRG1(+) ILC-2s significantly reduced worm burden. Furthermore, blocking PD-1 with an antibody increased KLRG1(+) ILC-2 cell number and reduced disease burden. Therefore, PD-1 is required for maintaining the number, and hence function, of KLRG1(+) ILC-2s.

引用

页码：1663 / 1678

页数：16

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