Selective deregulation in chemokine signaling pathways of CD4+CD25hiCD127lo/− regulatory T cells in human allergic asthma - 15/08/11
Reprint requests: Kari C. Nadeau, MD, PhD, Department of Pediatrics, Pulmonary Center of Excellence, Stanford University, Stanford, CA, 94305.Abstract |
Background |
CD4+CD25hiCD127lo/− regulatory T cells have been suggested to be critical regulators of inflammatory processes in allergic asthma. Recent studies reported a selective decrease in the frequency of regulatory T cells in the bronchoalveolar lavage fluid of allergic asthmatic (AA) subjects, prompting the possibility of defective recruitment of these cells to the airway in response to chemokines produced during asthmatic inflammation.
Objectives |
This study aimed to characterize the chemotactic profile of circulating regulatory T cells in AA subjects in response to chemokines abundantly produced in airway inflammation, such as CCL1, CCL17, and CCL22.
Methods |
The study was performed in a cohort of 26 AA, 16 healthy control, and 16 non-AA subjects. We used chemotaxis assays to evaluate cell migration, flow cytometry to examine chemokine receptor expression, and phospho-ELISA to study consequent signaling pathways in regulatory T cells.
Results |
Regulatory T cells, but not CD4+CD25−T cells, from AA subjects showed decreased chemotactic responses, specifically to CCL1, in comparison with their healthy control and non-AA counterparts. Decreased CCL1-mediated chemotaxis in AA regulatory T cells was associated with decreased phosphorylation of protein kinase B (AKT), a protein involved in chemokine intracellular signaling. Furthermore, the decreased chemotactic response to CCL1 in AA regulatory T cells significantly correlated with asthma severity and decreased pulmonary function in AA subjects.
Conclusions |
These results provide the first evidence of dysfunction in the chemokine signaling pathway in AA regulatory T cells.
Le texte complet de cet article est disponible en PDF.Key words : Allergic asthma, regulatory T cells, cell trafficking, cell signaling, CCL1, CCR8, AKT
Abbreviations used : AA, AKT, BALF, ERK1/2, HC, NA, Non-Treg, Phospho-AKT, PTEN, Treg
Plan
| Supported by grants from the Mary Hewitt Loveless Foundation, the Parker B. Francis Foundation, and the American Academy of Allergy, Asthma & Immunology. |
|
| Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest. |
Vol 123 - N° 4
P. 933 - avril 2009 Retour au numéro
Article précédent
- Combined sensitization of mice to extracts of dust mite, ragweed, and Aspergillus species breaks through tolerance and establishes chronic features of asthma
- Nicholas Goplen, M. Zunayet Karim, Qiaoling Liang, Magdalena M. Gorska, Sadee Rozario, Lei Guo, Rafeul Alam
- Adiposity, serum lipid levels, and allergic sensitization in Chinese men and women
- Fengxiu Ouyang, Rajesh Kumar, Jacqueline Pongracic, Rachel E. Story, Xin Liu, Binyan Wang, Houxun Xing, Xue Liu, Zhiping Li, Wenbin Zhang, Yaping Fang, Shanchun Zhang, Xiping Xu, Xiaobin Wang
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?