Commonality of the IL-4/IL-13 pathway in atopic diseases

被引:383
作者
Gandhi, Namita A. [1 ]
Pirozzi, Gianluca [2 ]
Graham, Neil M. H. [3 ]
机构
[1] Regeneron Pharmaceut Inc, Clin Sci, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA
[2] Sanofi, Res & Dev, Bridgewater, NJ USA
[3] Regeneron Pharmaceut Inc, Project Direct, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA
关键词
interleukin-4; interleukin-13; dupilumab; lebrikizumab; tralokinumab; Type; 2; pathway; asthma; atopic dermatitis; nasal polyposis; ACTIVATION-REGULATED CHEMOKINE; DOUBLE-BLIND; PERSISTENT ASTHMA; ADULT PATIENTS; SERUM THYMUS; INTERLEUKIN-4; RECEPTOR; ORAL CYCLOSPORINE; ALLERGIC DISEASES; STRUCTURAL BASIS; CLUSTER-ANALYSIS;
D O I
10.1080/1744666X.2017.1298443
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Introduction: Allergy results from an aberrant Type 2 inflammatory response, triggered by a wide range of environmental antigens (allergens) that lead to various immune responses, culminating in the production of immunoglobulin E (IgE). Two key cytokines, interleukin (IL)-4 and IL-13, are critical to the induction and perpetuation of the Type 2 response, and have been implicated in multiple atopic diseases.Area covered: This review summarizes recent milestone developments that have elucidated components of the pathogenesis of atopic diseases such as atopic dermatitis (AD), asthma, and chronic sinusitis with nasal polyposis (CSwNP).Expert commentary: Several therapeutic agents that selectively target potentiators of the Type 2 pathway have shown efficacy in one or more of these atopic diseases, but few agents have proven to be broadly applicable across all three atopic diseases. Dupilumab, a human monoclonal antibody that simultaneously inhibits signaling of IL-4 and IL-13, has demonstrated significant clinical efficacy in AD, asthma, and CSwNP. The fact that these diseases often occur as comorbidities and respond to the same therapy suggests that there is a common underlying pathogenic pathway, and that IL-4 and IL-13 cytokines are central to regulating the pathogenesis of these atopic diseases.
引用
收藏
页码:425 / 437
页数:13
相关论文
共 133 条
[71]   Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system [J].
LaPorte, Sherry L. ;
Juo, Z. Sean ;
Vaclavikova, Jana ;
Colf, Leremy A. ;
Qi, Xiulan ;
Heller, Nicola M. ;
Keegan, Achsah D. ;
Garcia, K. Christopher .
CELL, 2008, 132 (02) :259-272
[72]   Does the severity of atopic dermatitis correlate with serum IgE levels? [J].
Laske, N ;
Niggemann, B .
PEDIATRIC ALLERGY AND IMMUNOLOGY, 2004, 15 (01) :86-88
[73]   New Insights into Atopic Dermatitis: Role of Skin Barrier and Immune Dysregulation [J].
Leung, Donald Y. M. .
ALLERGOLOGY INTERNATIONAL, 2013, 62 (02) :151-161
[74]  
LOWENTHAL JW, 1988, J IMMUNOL, V140, P456
[75]  
Lübbe J, 2003, AM J CLIN DERMATOL, V4, P641
[76]  
MacGlashan DW, 1997, J IMMUNOL, V158, P1438
[77]   Targeting Interleukin-4 in Asthma: Lost in Translation? [J].
Maes, Tania ;
Joos, Guy F. ;
Brusselle, Guy G. .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2012, 47 (03) :261-270
[78]   Epigenetic modifications: mechanisms of disease and biomarkers of food allergy [J].
Martino, David J. ;
Saffery, Richard ;
Allen, Katrina J. ;
Prescott, Susan L. .
CURRENT OPINION IN IMMUNOLOGY, 2016, 42 :9-15
[79]   Strategies targeting the IL-4/IL-13 axes in disease [J].
May, Richard D. ;
Fung, Michael .
CYTOKINE, 2015, 75 (01) :89-116
[80]   INTERLEUKIN-13, A T-CELL-DERIVED CYTOKINE THAT REGULATES HUMAN MONOCYTE AND B-CELL FUNCTION [J].
MCKENZIE, ANJ ;
CULPEPPER, JA ;
MALEFYT, RD ;
BRIERE, F ;
PUNNONEN, J ;
AVERSA, G ;
SATO, A ;
DANG, W ;
COCKS, BG ;
MENON, S ;
DEVRIES, JE ;
BANCHEREAU, J ;
ZURAWSKI, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (08) :3735-3739