Article

CD69 controls the pathogenesis of allergic airway inflammation.

Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
The Journal of Immunology (impact factor: 5.79). 11/2009; 183(12):8203-15. DOI:10.4049/jimmunol.0900646 pp.8203-15
Source: PubMed

ABSTRACT Airway inflammation and airway hyperresponsiveness are central issues in the pathogenesis of asthma. CD69 is a membrane molecule transiently expressed on activated lymphocytes, and its selective expression in inflammatory infiltrates suggests that it plays a role in the pathogenesis of inflammatory diseases. In CD69-deficient mice, OVA-induced eosinophilic airway inflammation, mucus hyperproduction, and airway hyperresponsiveness were attenuated. Cell transfer of Ag-primed wild-type but not CD69-deficient CD4 T cells restored the induction of allergic inflammation in CD69-deficient mice, indicating a critical role of CD69 expressed on CD4 T cells. Th2 responses induced by CD69-deficient CD4 T cells in the lung were attenuated, and the migration of CD4 T cells into the asthmatic lung was severely compromised. The expression of VCAM-1 was also substantially altered, suggesting the involvement of VCAM-1 in the CD69-dependent migration of Th2 cells into the asthmatic lung. Interestingly, the administration of anti-CD69 Ab inhibited the induction of the OVA-induced airway inflammation and hyperresponsiveness. This inhibitory effect induced by the CD69 mAb was observed even after the airway challenge with OVA. These results indicate that CD69 plays a crucial role in the pathogenesis of allergen-induced eosinophilic airway inflammation and hyperresponsiveness and that CD69 could be a possible therapeutic target for asthmatic patients.

0 0
 · 
0 Bookmarks
 · 
63 Views
  • Source
    Article: The asthma candidate gene NPSR1 mediates isoform specific downstream signalling.
    Christina Orsmark Pietras, Johanna Vendelin, Francesca Anedda, Sara Bruce, Mikael Adner, Lilli Sundman, Ville Pulkkinen, Harri Alenius, Mauro D'Amato, Cilla Söderhäll, Juha Kere
    [show abstract] [hide abstract]
    ABSTRACT: Neuropeptide S Receptor 1 (NPSR1, GPRA, GPR154) was first identified as an asthma candidate gene through positional cloning and has since been replicated as an asthma and allergy susceptibility gene in several independent association studies. In humans, NPSR1 encodes two G protein-coupled receptor variants, NPSR1-A and NPSR1-B, with unique intracellular C-termini. Both isoforms show distinct expression pattern in asthmatic airways. Although NPSR1-A has been extensively studied, functional differences and properties of NPSR1-B have not yet been clearly examined. Our objective was to investigate downstream signalling properties of NPSR1-B and functional differences between NPSR1-A and NPSR1-B. HEK-293 cells transiently overexpressing NPSR1-A or NPSR1-B were stimulated with the ligand neuropeptide S (NPS) and downstream signalling effects were monitored by genome-scale affymetrix expression-arrays. The results were verified by NPS concentration-response and time series analysis using qRT-PCR, cAMP and Ca²⁺ assays, and cAMP/PKA, MAPK/JNK and MAPK/ERK pathway specific reporter assays. NPSR1-B signalled through the same pathways and regulated the same genes as NPSR1-A, but NPSR1-B yielded lower induction on effector genes than NPSR1-A, with one notable exception, CD69, a marker of regulatory T cells. We conclude that NPSR1-B is regulating essentially identical set of genes as NPSR1-A, with few, but possibly important exceptions, and that NPSR1-A induces stronger signalling effects than NPSR1-B. Our findings suggest an isoform-specific link to pathogenetic processes in asthma and allergy.
    BMC Pulmonary Medicine 06/2011; 11:39. · 1.33 Impact Factor
  • Source
    Article: Attenuation of lung inflammation and fibrosis in CD69-deficient mice after intratracheal bleomycin.
    Keita Yamauchi, Yoshitoshi Kasuya, Fuminobu Kuroda, Kensuke Tanaka, Junichi Tsuyusaki, Shunsuke Ishizaki, Hirofumi Matsunaga, Chiaki Iwamura, Toshinori Nakayama, Koichiro Tatsumi
    [show abstract] [hide abstract]
    ABSTRACT: Cluster of differentiation 69 (CD69), an early activation marker antigen on T and B cells, is also expressed on activated macrophages and neutrophils, suggesting that CD69 may play a role in inflammatory diseases. To determine the effect of CD69 deficiency on bleomycin(BLM)-induced lung injury, we evaluated the inflammatory response following intratracheal BLM administration and the subsequent fibrotic changes in wild type (WT) and CD69-deficient (CD69-/-) mice. The mice received a single dose of 3 mg/kg body weight of BLM and were sacrificed at 7 or 14 days post-instillation (dpi). Lung inflammation in the acute phase (7 dpi) was investigated by differential cell counts and cytokine array analyses of bronchoalveolar lavage fluid. In addition, lung fibrotic changes were evaluated at 14 dpi by histopathology and collagen assays. We also used reverse transcription polymerase chain reaction to measure the mRNA expression level of transforming growth factor β1 (TGF-β1) in the lungs of BLM-treated mice. CD69-/- mice exhibited less lung damage than WT mice, as shown by reductions in the following indices: (1) loss of body weight, (2) wet/dry ratio of lung, (3) cytokine levels in BALF, (4) histological evidence of lung injury, (5) lung collagen deposition, and (6) TGF-β1 mRNA expression in the lung. The present study clearly demonstrates that CD69 plays an important role in the progression of lung injury induced by BLM.
    Respiratory research 01/2011; 12:131. · 3.36 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

Ag-primed wild-type
 
Airway inflammation
 
allergen-induced eosinophilic airway inflammation
 
allergic inflammation
 
anti-CD69 Ab inhibited
 
asthmatic lung
 
asthmatic patients
 
CD4 T cells
 
CD69-deficient CD4 T cells
 
CD69-deficient mice
 
CD69-dependent migration
 
Cell transfer
 
inhibitory effect induced
 
membrane molecule transiently
 
mucus hyperproduction
 
OVA-induced airway inflammation
 
OVA-induced eosinophilic airway inflammation
 
possible therapeutic target
 
Th2 cells
 
Th2 responses induced