Activation of Peripheral Th17 Lymphocytes in Patients with Asthma

被引:41
作者
Wong, C. K. [1 ]
Lun, S. W. M. [1 ]
Ko, F. W. S. [2 ]
Wong, P. T. Y. [1 ]
Hu, S. Q. [1 ]
Chan, I. H. S. [1 ]
Hui, D. S. C. [2 ]
Lam, C. W. K. [1 ,3 ]
机构
[1] Chinese Univ Hong Kong, Dept Chem Pathol, Shatin, Hong Kong, Peoples R China
[2] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Shatin, Hong Kong, Peoples R China
[3] Macau Univ Sci & Technol, Macau Inst Appl Res Med & Hlth, Taipa, Macau, Peoples R China
关键词
Asthma; CCR6; IL-22; Th17; cells; SYSTEMIC-LUPUS-ERYTHEMATOSUS; RHEUMATOID-ARTHRITIS; GENE-EXPRESSION; IFN-GAMMA; T-CELLS; IL-17; CHEMOKINE; CYTOKINE; DIFFERENTIATION; INFLAMMATION;
D O I
10.1080/08820130903062756
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
A recently identified interleukin (IL)-17-producing T-helper (Th) lymphocyte subset, which comprises Th17 cells producing hallmark cytokines IL-17A, IL-17F and IL-22, is involved in chronic inflammatory diseases. Elevated gene and protein expressions of IL-17 are manifested in allergic asthma. We further characterized the activation of Th17 cells in asthmatic patients. Peripheral blood mononuclear cells (PBMC) were purified from 31 asthmatic patients and 20 sex-and age-matched control subjects. The number of IL-17A secreting cells in peripheral blood was enumerated by enzyme-linked immunosorbent spot assay. Cell surface expression of Th17-related chemokine receptor CCR6, and plasma level of IL-17A, IL-17F and IL-22, and ex vivo production of IL-17A and IL-22 were measured by flow cytometry and enzyme-linked immunosorbent assay, respectively. The number of peripheral Th17 lymphocytes, expression of CCR6 on Th cells, and ex vivo IL-23, anti-CD3 and anti-CD28 induced production of IL-22 by PBMC were significantly elevated in asthmatic patients compared with control subjects (all p < 0.01). This clinical study further confirmed increased number of peripheral Th17 lymphocytes and cell surface expression of CCR6 receptors on Th cells in asthmatic patients. Pro-inflammatory cytokine IL-23 can exacerbate disease severity by activating pathogenic Th17 lymphocytes to release downstream inflammatory cytokine IL-22 in asthma.
引用
收藏
页码:652 / 664
页数:13
相关论文
共 41 条
[1]   Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17-producing human T helper cells [J].
Acosta-Rodriguez, Eva V. ;
Napolitani, Giorgio ;
Lanzavecchia, Antonio ;
Sallusto, Federica .
NATURE IMMUNOLOGY, 2007, 8 (09) :942-949
[2]   Acinar cells of the pancreas are a target of interleukin-22 [J].
Aggarwal, S ;
Xie, MH ;
Maruoka, M ;
Foster, J ;
Gurney, AL .
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 2001, 21 (12) :1047-1053
[3]   Phenotypic and functional features of human Th17 cells [J].
Annunziato, Francesco ;
Cosmi, Lorenzo ;
Santarlasci, Veronica ;
Maggi, Laura ;
Liotta, Francesco ;
Mazzinghi, Benedetta ;
Parente, Eliana ;
Fili, Lucia ;
Ferri, Simona ;
Frosali, Francesca ;
Giudici, Francesco ;
Romagnani, Paola ;
Parronchi, Paola ;
Tonelli, Francesco ;
Maggi, Enrico ;
Romagnani, Sergio .
JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (08) :1849-1861
[5]   IL-22 inhibits epidermal differentiation and induces proinflammatory gene expression and migration of human keratinocytes [J].
Boniface, K ;
Bernard, FX ;
Garcia, M ;
Gurney, AL ;
Lecron, JC ;
Morel, F .
JOURNAL OF IMMUNOLOGY, 2005, 174 (06) :3695-3702
[6]   The development of inflammatory TH-17 cells requires interferon-regulatory factor 4 [J].
Bruestle, Anne ;
Heink, Sylvia ;
Huber, Magdalena ;
Rosenplaenter, Christine ;
Stadelmann, Christine ;
Yu, Philipp ;
Arpaia, Enrico ;
Mak, Tak W. ;
Kamradt, Thomas ;
Lohoff, Michael .
NATURE IMMUNOLOGY, 2007, 8 (09) :958-966
[7]   IL-17 mRNA in sputum of asthmatic patients: linking T cell driven inflammation and granulocytic influx? [J].
Bullens, Dominique M. A. ;
Truyen, Els ;
Coteur, Liesbeth ;
Dilissen, Ellen ;
Hellings, Peter W. ;
Dupont, Lieven J. ;
Ceuppens, Jan L. .
RESPIRATORY RESEARCH, 2006, 7 (1)
[8]   Enhancing effect of IL-1, IL-17, and TNF-α on macrophage inflammatory protein-3α production in rheumatoid arthritis:: Regulation by soluble receptors and Th2 cytokines [J].
Chabaud, M ;
Page, G ;
Miossec, P .
JOURNAL OF IMMUNOLOGY, 2001, 167 (10) :6015-6020
[9]  
CHANYEUNG M, 1993, AM REV RESPIR DIS, V147, P1056
[10]   Stimulation of airway mucin gene expression by interleukin (IL)-17 through IL-6 paracrine/autocrine loop [J].
Chen, Y ;
Thai, P ;
Zhao, YH ;
Ho, YS ;
DeSouza, MM ;
Wu, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (19) :17036-17043