Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity.
Thymic stromal lymphopoietin (TSLP) is said to increase expression of chemokines attracting Th2 T cells. We hypothesized that asthma is characterized by elevated bronchial mucosal expression of TSLP and Th2-attracting, but not Th1-attracting, chemokines as compared with controls, with selective accumulation of cells bearing receptors for these chemokines. We used in situ hybridization and immunohistochemistry to examine the expression and cellular provenance of TSLP, Th2-attracting (thymus and activation-regulated chemokine (TARC)/CCL17, macrophage-derived chemokine (MDC)/CCL22, I-309/CCL1) and Th1-attracting (IFN-gamma-inducible protein 10 (IP-10)/CXCL10, IFN-inducible T cell alpha-chemoattractant (I-TAC)/CXCL11) chemokines and expression of their receptors CCR4, CCR8, and CXCR3 in bronchial biopsies from 20 asthmatics and 15 normal controls. The numbers of cells within the bronchial epithelium and submucosa expressing mRNA for TSLP, TARC/CCL17, MDC/CCL22, and IP-10/CXCL10, but not I-TAC/CXCL11 and I-309/CCL1, were significantly increased in asthmatics as compared with controls (p </= 0.018). TSLP and TARC/CCL17 expression correlated with airway obstruction. Although the total numbers of cells expressing CCR4, CCR8, and CXCR3 did not significantly differ in the asthmatics and controls, there was evidence of selective infiltration of CD4(+)/CCR4(+) T cells in the asthmatic biopsies which correlated with TARC and MDC expression and airway obstruction. Epithelial cells, endothelial cells, neutrophils, macrophages, and mast cells were significant sources of TSLP and chemokines. Our data implicate TSLP, TARC/CCL17, MDC/CCL22, and IP-10/CXCL10 in asthma pathogenesis. These may act partly through selective development and retention, or recruitment of Th2 cells bearing their receptors.
Ying
Sun
S
Department of Asthma, Allergy and Respiratory Science, Guy's, King's and St. Thomas' (GKT) School of Medicine, London, United Kingdom. ying.sun@kcl.ac.uk
O'Connor
Brian
B
Ratoff
Jonathan
J
Meng
Qiu
Q
Mallett
Kirsty
K
Cousins
David
D
Robinson
Douglas
D
Zhang
Guizhen
G
Zhao
Jisheng
J
Lee
Tak H
TH
Corrigan
Chris
C
D000328:Adult; D000368:Aged; D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D002465:Cell Movement / Q000276:immunology; D054402:Chemokine CCL1; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D019707:Receptors, Chemokine / Q000096:biosynthesis; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology*; D000094632:Thymic Stromal Lymphopoietin
C065971:CCL1 protein, human; C106230:CCL17 protein, human; C515482:CCL22 protein, human; C515202:CXCL11 protein, human; D054402:Chemokine CCL1; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D019742:Chemokines, CC; D019743:Chemokines, CXC; D016207:Cytokines; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D000094632:Thymic Stromal Lymphopoietin