TH2 and TH17 inflammatory pathways are reciprocally regulated in asthma

被引：422

作者：

Choy, David F. ^{[1
]}

Hart, Kevin M. ^{[2
]}

Borthwick, Lee A. ^{[3
]}

Shikotra, Aarti ^{[4
]}

Nagarkar, Deepti R. ^{[1
]}

Siddiqui, Salman ^{[4
]}

Jia, Guiquan ^{[1
]}

Ohri, Chandra M. ^{[4
]}

Doran, Emma ^{[1
,5
]}

Vannella, Kevin M. ^{[2
]}

Butler, Claire A. ^{[5
]}

Hargadon, Beverley ^{[4
]}

Sciurba, Joshua C. ^{[2
]}

Gieseck, Richard L. ^{[2
]}

Thompson, Robert W. ^{[2
]}

White, Sandra ^{[2
]}

Abbas, Alexander R. ^{[1
]}

Jackman, Janet ^{[1
]}

Wu, Lawren C. ^{[1
]}

Egen, Jackson G. ^{[1
]}

Heaney, Liam G. ^{[5
]}

Ramalingam, Thirumalai R. ^{[2
]}

Arron, Joseph R. ^{[1
]}

Wynn, Thomas A. ^{[2
]}

Bradding, Peter ^{[4
]}

机构：

[1] Genentech Inc, San Francisco, CA 94080 USA

[2] NIAID, Program Tissue Immun & Repair, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA

[3] Newcastle Univ, Inst Cellular Med, Tissue Fibrosis & Repair Grp, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

[4] Univ Leicester, Inst Lung Hlth, Dept Infect Immun & Inflammat, Leicester LE3 9QP, Leics, England

[5] Queens Univ Belfast, Ctr Infect & Immun, Belfast BT9 7AB, Antrim, North Ireland

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2015年 / 7卷 / 301期

关键词：

NECROSIS-FACTOR-ALPHA; THYMIC STROMAL LYMPHOPOIETIN; AIRWAY HYPERRESPONSIVENESS; CLUSTER-ANALYSIS; CELLS; IL-13; INTERLEUKIN-17; IDENTIFICATION; EXACERBATIONS; EXPRESSION;

D O I：

10.1126/scitranslmed.aab3142

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Increasing evidence suggests that asthma is a heterogeneous disorder regulated by distinct molecular mechanisms. In a cross-sectional study of asthmatics of varying severity (n = 51), endobronchial tissue gene expression analysis revealed three major patient clusters: T(H)2-high, T(H)17-high, and T(H)2/17-low. T(H)2-high and T(H)17-high patterns were mutually exclusive in individual patient samples, and their gene signatures were inversely correlated and differentially regulated by interleukin-13 (IL-13) and IL-17A. To understand this dichotomous pattern of T helper 2 (T(H)2) and T(H)17 signatures, we investigated the potential of type 2 cytokine suppression in promoting T(H)17 responses in a preclinical model of allergen-induced asthma. Neutralization of IL-4 and/or IL-13 resulted in increased T(H)17 cells and neutrophilic inflammation in the lung. However, neutralization of IL-13 and IL-17 protected mice from eosinophilia, mucus hyperplasia, and airway hyperreactivity and abolished the neutrophilic inflammation, suggesting that combination therapies targeting both pathways may maximize therapeutic efficacy across a patient population comprising both T(H)2 and T(H)17 endotypes.

引用

页数：10

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