Expression and cellular provenance of thymic stromal lymphopoietin and chemokines in patients with severe asthma and chronic obstructive pulmonary disease.
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.
Ying
Sun
S
King's College London, Division of Asthma, Allergy and Lung Biology, Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom. ying.sun@kcl.ac.uk
O'Connor
Brian
B
Ratoff
Jonathan
J
Meng
Qiu
Q
Fang
Cailong
C
Cousins
David
D
Zhang
Guizhen
G
Gu
Shuyan
S
Gao
Zhongli
Z
Shamji
Betty
B
Edwards
Matthew J
MJ
Lee
Tak H
TH
Corrigan
Chris J
CJ
D051722:ADAM Proteins / Q000096:biosynthesis; D000328:Adult; D000368:Aged; D001249:Asthma / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D054402:Chemokine CCL1 / Q000096:biosynthesis; D054414:Chemokine CCL17 / Q000096:biosynthesis; D054357:Chemokine CXCL10 / Q000096:biosynthesis; D054371:Chemokine CXCL11 / Q000096:biosynthesis; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis* / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis; D000094632:Thymic Stromal Lymphopoietin
C065971:CCL1 protein, human; C106230:CCL17 protein, human; C114753:CXCL10 protein, human; C515202:CXCL11 protein, human; D054402:Chemokine CCL1; D054414:Chemokine CCL17; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D018925:Chemokines; D016207:Cytokines; D025521:Tumor Suppressor Proteins; D051722:ADAM Proteins; C090222:ADAM11 protein, human; D000094632:Thymic Stromal Lymphopoietin