New insights into the generation of Th2 immunity and potential therapeutic targets for the treatment of asthma

被引:49
作者
Kaiko, Gerard E. [1 ,2 ]
Foster, Paul S. [1 ,2 ]
机构
[1] Univ Newcastle, Fac Hlth, Sch Biomed Sci & Pharm, Ctr Asthma & Resp Dis, Newcastle, NSW 2300, Australia
[2] Cooperat Res Ctr CRC Asthma & Airways, Newcastle, NSW, Australia
基金
澳大利亚国家健康与医学研究理事会;
关键词
allergens; asthma; basophil; IL-25; IL-33; nuocyte; Th2; Th9; TSLP; virus; THYMIC STROMAL LYMPHOPOIETIN; DENDRITIC CELLS; AIRWAY HYPERRESPONSIVENESS; ALLERGIC INFLAMMATION; EPITHELIAL-CELLS; PROMOTES; IL-25; POPULATION; EXPRESSION; BASOPHILS;
D O I
10.1097/ACI.0b013e328342322f
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Purpose of review Asthma is a heterogeneous disease with unknown cause; however, allergic asthma is driven largely by Th2-type immune responses. The pathways that interact to induce Th1 and Th17-type immune responses are well understood; however, until recently the innate immune pathways involved in the induction of Th2-type immunity were unknown. In this review we sought to outline many of the recent advances in uncovering the cell and molecular mechanisms that generate Th2 responses. Recent findings It is clear that the Th2 pathway can no longer be considered a 'default pathway' of the lung immune system as multiple cells and cytokines have now been identified that work to actively instruct Th2 differentiation. Basophils and dendritic cells have been investigated for their critical role in Th2 induction, and newly identified cell subsets have also been shown to play an important function in Th2 responses. The identification of the Th2-inducing cytokines IL-25, IL-33 and thymic stromal lymphopoietin has also accelerated studies examining the development of Th2 responses in asthma. Summary Studies of the role played by the innate immune system in the induction of Th2 responses have begun to unravel the cellular and molecular mechanisms potentially underlying the pathogenesis of allergic asthma. Further study in this area may lead to the discovery of new therapeutics for the treatment of allergic disease.
引用
收藏
页码:39 / 45
页数:7
相关论文
共 49 条
[1]   CD34+ hemopoietic progenitor cells are potent effectors of allergic inflammation [J].
Allakhverdi, Zoulfia ;
Comeau, Michael R. ;
Smith, Dirk E. ;
Toy, Dean ;
Endam, Leandra Mfuna ;
Desrosiers, Martin ;
Liu, Yong-Jun ;
Howie, Karen J. ;
Denburg, Judah A. ;
Gauvreau, Gail M. ;
Delespesse, Guy .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2009, 123 (02) :472-478
[2]   Instruction of distinct CD4 T helper cell fates by different notch ligands on antigen-presenting cells [J].
Amsen, D ;
Blander, JM ;
Lee, GR ;
Tanigaki, K ;
Honjo, T ;
Flavell, RA .
CELL, 2004, 117 (04) :515-526
[3]   Interleukin 25 promotes the initiation of proallergic type 2 responses [J].
Angkasekwinai, Pornpimon ;
Park, Heon ;
Wang, Yui-Hsi ;
Wang, Yi-Hong ;
Chang, Seon Hee ;
Corry, David B. ;
Liu, Yong-Jun ;
Zhu, Zhou ;
Dong, Chen .
JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (07) :1509-1517
[4]   Regulation of IL-9 expression by IL-25 signaling [J].
Angkasekwinai, Pornpimon ;
Chang, Seon Hee ;
Thapa, Manoj ;
Watarai, Hiroshi ;
Dong, Chen .
NATURE IMMUNOLOGY, 2010, 11 (03) :250-U9
[5]  
Antoniu SA, 2010, CURR OPIN MOL THER, V12, P233
[6]   Blocking IL-25 prevents airway hyperresponsiveness in allergic asthma [J].
Ballantyne, Sarah J. ;
Barlow, Jillian L. ;
Jolin, Helen E. ;
Nath, Puneeta ;
Williams, Alison S. ;
Chung, Kian Fan ;
Sturton, Graham ;
Wong, See Heng ;
McKenzie, Andrew N. J. .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2007, 120 (06) :1324-1331
[7]   Immune Sensing of Aspergillus fumigatus Proteins, Glycolipids, and Polysaccharides and the Impact on Th Immunity and Vaccination [J].
Bozza, Silvia ;
Clavaud, Cecile ;
Giovannini, Gloria ;
Fontaine, Thierry ;
Beauvais, Anne ;
Sarfati, Jacqueline ;
D'Angelo, Carmen ;
Perruccio, Katia ;
Bonifazi, Pierluigi ;
Zagarella, Silvia ;
Moretti, Silvia ;
Bistoni, Francesco ;
Latge, Jean-Paul ;
Romani, Luigina .
JOURNAL OF IMMUNOLOGY, 2009, 183 (04) :2407-2414
[8]   Histamine polarizes human dendritic cells into Th2 cell-promoting effector dendritic cells [J].
Caron, G ;
Delneste, Y ;
Roelandts, E ;
Duez, C ;
Bonnefoy, JY ;
Pestel, J ;
Jeannin, P .
JOURNAL OF IMMUNOLOGY, 2001, 167 (07) :3682-3686
[9]   The Adaptor Protein CIKS/Act1 Is Essential for IL-25-Mediated Allergic Airway Inflammation [J].
Claudio, Estefania ;
Sonder, Soren Ulrik ;
Saret, Sun ;
Carvalho, Gabrielle ;
Ramalingam, Thirumalai R. ;
Wynn, Thomas A. ;
Chariot, Alain ;
Garcia-Perganeda, Antonio ;
Leonardi, Antonio ;
Paun, Andrea ;
Chen, Amy ;
Ren, Nina Y. ;
Wang, Hongshan ;
Siebenlist, Ulrich .
JOURNAL OF IMMUNOLOGY, 2009, 182 (03) :1617-1630
[10]   Sputum CD34+IL-5Rα+ cells increase after allergen -: Evidence for in situ eosinophilopoiesis [J].
Dorman, SC ;
Efthimiadis, A ;
Babirad, I ;
Watson, RM ;
Denburg, JA ;
Hargreave, FE ;
O'Byrne, PM ;
Sehmi, R .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2004, 169 (05) :573-577