Synergistic activation of pro-inflammatory type-2 CD8+ T lymphocytes by lipid mediators in severe eosinophilic asthma

被引：47

作者：

Hilvering, Bart ^{[1
,2
]}

Hinks, Timothy S. C. ^{[1
,2
,3
]}

Stoger, Linda ^{[1
,2
]}

Marchi, Emanuele ^{[4
,5
]}

Salimi, Maryam ^{[6
]}

Shrimanker, Rahul ^{[1
,2
]}

Liu, Wei ^{[1
,2
]}

Chen, Wentao ^{[1
,2
]}

Luo, Jian ^{[1
,2
]}

Go, Simei ^{[1
,2
]}

Powell, Timothy ^{[1
,2
]}

Cane, Jennifer ^{[1
,2
]}

Thulborn, Samantha ^{[1
,2
]}

Kurioka, Ayako ^{[4
,5
]}

Leng, Tianqi ^{[4
,5
]}

Matthews, Jamie ^{[4
,5
]}

Connolly, Clare ^{[1
,2
]}

Borg, Catherine ^{[1
,2
]}

Bafadhel, Mona ^{[1
,2
]}

Willberg, Christian B. ^{[4
,5
]}

Ramasamy, Adaikalavan ^{[7
]}

Djukanovic, Ratko ^{[3
,8
]}

Ogg, Graham ^{[6
]}

Pavord, Ian D. ^{[1
,2
]}

Klenerman, Paul ^{[4
,5
]}

Xue, Luzheng ^{[1
,2
]}

机构：

[1] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Med, Resp Med Unit, Oxford, England

[2] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Med, Oxford Biomed Res Ctr, Oxford, England

[3] Univ Southampton, Fac Med, Southampton Univ Hosp, Clin & Expt Sci, Southampton, Hants, England

[4] Univ Oxford, Nuffield Dept Med, Translat Gastroenterol Unit, South Parks Rd, Oxford, England

[5] Univ Oxford, Nuffield Dept Med, Peter Medawar Bldg,South Parks Rd, Oxford, England

[6] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, MRC Human Immunol Unit, Oxford, England

[7] Univ Oxford, Jenner Inst, Transcript Core Facil, Oxford, England

[8] Southampton Univ Hosp, NIHR Southampton Resp Biomed Res Unit, Southampton, Hants, England

来源：

MUCOSAL IMMUNOLOGY | 2018年 / 11卷 / 05期

基金：

英国惠康基金;

关键词：

PLACEBO-CONTROLLED TRIAL; INNATE LYMPHOID-CELLS; HUMAN TH2 CELLS; PROSTAGLANDIN D-2; AIRWAY HYPERRESPONSIVENESS; CYTOKINE PRODUCTION; NASAL POLYPS; DOUBLE-BLIND; EXPRESSION; CRTH2;

D O I：

10.1038/s41385-018-0049-9

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Human type-2 CD8(+) T cells are a cell population with potentially important roles in allergic disease. We investigated this in the context of severe asthma with persistent airway eosinophilia-a phenotype associated with high exacerbation risk and responsiveness to type-2 cytokine-targeted therapies. In two independent cohorts we show that, in contrast to Th2 cells, type-2 cytokine-secreting CD8(+)CRTH2(+) (Tc2) cells are enriched in blood and airways in severe eosinophilic asthma. Concentrations of prostaglandin D-2 (PGD2) and cysteinyl leukotriene E-4 (LTE4) are also increased in the airways of the same group of patients. In vitro PGD(2) and LTE4 function synergistically to trigger Tc2 cell recruitment and activation in a TCR-independent manner. These lipids regulate diverse genes in Tc2 cells inducing type-2 cytokines and many other pro-inflammatory cytokines and chemokines, which could contribute to eosinophilia. These findings are consistent with an important innate-like role for human Tc2 cells in severe eosinophilic asthma and suggest a potential target for therapeutic intervention in this and other diseases.

引用

页码：1408 / 1419

页数：12

共 54 条

[51] Prostaglandin D2 activates group 2 innate lymphoid cells through chemoattractant receptor-homologous molecule expressed on TH2 cells [J].

Xue, Luzheng ;

Salimi, Maryam ;

Panse, Isabel ;

Mjosberg, Jenny M. ;

McKenzie, Andrew N. J. ;

Spits, Hergen ;

Klenerman, Paul ;

Ogg, Graham .

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2014, 133 (04) :1184-+

[52] Leukotriene E4 Activates Human Th2 Cells for Exaggerated Proinflammatory Cytokine Production in Response to Prostaglandin D2 [J].

Xue, Luzheng ;

Barrow, Anna ;

Fleming, Vicki M. ;

Hunter, Michael G. ;

Ogg, Graham ;

Klenerman, Paul ;

Pettipher, Roy .

JOURNAL OF IMMUNOLOGY, 2012, 188 (02) :694-702

[53] Novel Function of CRTH2 in Preventing Apoptosis of Human Th2 Cells through Activation of the Phosphatidylinositol 3-Kinase Pathway [J].

Xue, Luzheng ;

Barrow, Anna ;

Pettipher, Roy .

JOURNAL OF IMMUNOLOGY, 2009, 182 (12) :7580-7586

[54] Prostaglandin D2 causes preferential induction of proinflammatory Th2 cytokine production through an action on chemoattractant receptor-like molecule expressed on Th2 cells [J].

Xue, LZ ;

Gyles, SL ;

Wettey, FR ;

Gazi, L ;

Townsend, E ;

Hunter, MG ;

Pettipher, R .

JOURNAL OF IMMUNOLOGY, 2005, 175 (10) :6531-6536

← 1 2 3 4 5 6 →