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* King’s College London, Division of Asthma, Allergy and Lung Biology, Medical Research Council and Asthma U.K. Centre in Allergic Mechanisms of Asthma, London, United Kingdom;
Department of Central Research, Third Clinical College, Jilin University, Changchun, China; and
Respiratory Disease Area, Novartis Institute of Biomedical Research, Horsham, United Kingdom
Asthma and chronic obstructive pulmonary disease (COPD) are associated with Th2 and Th1 differentiated T cells. The cytokine thymic stromal lymphopoietin (TSLP) promotes differentiation of Th2 T cells and secretion of chemokines which preferentially attract them. We hypothesized that there is distinct airways expression of TSLP and chemokines which preferentially attract Th1- and Th2-type T cells, and influx of T cells bearing their receptors in asthma and COPD. In situ hybridization, immunohistochemistry, and ELISA were used to examine the expression and cellular provenance of TSLP, Th2-attracting (TARC/CCL17, MDC/CCL22, I-309/CCL1), and Th1-attracting (IP-10/CXCL10, I-TAC/CXCL11) chemokines in the bronchial mucosa and bronchoalveolar lavage fluid of subjects with moderate/severe asthma, COPD, and controls. Cells expressing mRNA encoding TSLP, TARC/CCL17, MDC/CCL22, and IP-10/CXCL10, but not I-TAC/CXCL11 and I-309/CCL1, were significantly increased in severe asthma and COPD as compared with non-smoker controls (p < 0.02). This pattern was reflected in bronchoalveolar lavage fluid protein concentrations. Expression of the same chemokines was also increased in ex- and current smokers. The cellular sources of TSLP and chemokines were strikingly similar in severe asthma and COPD. The numbers of total bronchial mucosal T cells expressing the chemokine receptors CCR4, CCR8, and CXCR3 did not significantly differ in asthma, COPD, and controls. Both asthma and COPD are associated with elevated bronchial mucosal expression of TSLP and the same Th1- and Th2-attracting chemokines. Increased expression of these chemokines is not, however, associated with selective accumulation of T cells bearing their receptors.
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1 This work was supported in part by the Central Research Fund of the University of London, Asthma U.K., and Department of Asthma, Allergy and Respiratory Science, King’s College London. The authors acknowledge financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London.
2 Address correspondence and reprint requests to Dr. Sun Ying, Department of Asthma, Allergy and Respiratory Science, 5th Floor, Tower Wing, Guy’s Hospital, King’s College London, SE1 9RT, U.K. E-mail address: ying.sun{at}kcl.ac.uk
3 Abbreviations used in this paper: COPD, chronic obstructive pulmonary disease; TSLP, thymic stromal lymphopoietin; BAL, bronchoalveolar lavage; FEV1, forced expiratory volume in the first second; ISH, in situ hybridization; IHC, immunohistochemistry.
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