Expression of the T-cell chemoattractant chemokine lymphotactin in Crohn's disease.
Recruitment of lymphocytes is a prominent feature of the inflammatory process in Crohn's disease (CD). The present study was undertaken to investigate the expression of the novel lymphocyte-specific chemoattractant lymphotactin (Lptn) as a potential regulatory factor for the recruitment of T cells in CD. The expression of Lptn mRNA was quantified in resection specimens of patients with CD in comparison to normal controls without signs of inflammation by real-time quantitative reverse transcriptase-polymerase chain reaction and localized by nonradioactive in situ hybridization. Furthermore, the phenotype of cells expressing Lptn mRNA was characterized. In contrast to normal controls Lptn mRNA was significantly increased in tissue samples affected by CD. Cells expressing Lptn were identified as T cells, mast cells, and unexpectedly dendritic cells. Lptn mRNA was found to be up-regulated on stimulation with phorbol-12-myristate-13-acetate and concanavalin A in T cells isolated from peripheral blood, which could be prevented by dexamethasone, cyclosporine A, and FK506. A similar regulation mechanism could be identified for the Lptn receptor GPR-5 in peripheral T cells. In addition, Lptn mRNA expression could be induced in mature monocyte-derived dendritic cells. The results indicate that local expression of Lptn by activated T cells and to a lesser extent by mast cells and dendritic cells represents a key regulator for lymphocyte trafficking and maintenance of the inflammatory process observed in CD, which might be partly mediated through an autocrine/paracrine pathway of activated T cells.
Middel
P
P
Department of Pathology, Georg-August University of Göttingen, Göttingen, Germany. pmiddel@med.uni-goettingen.de
Thelen
P
P
Blaschke
S
S
Polzien
F
F
Reich
K
K
Blaschke
V
V
Wrede
A
A
Hummel
K M
KM
Gunawan
B
B
Radzun
H J
HJ
D002454:Cell Differentiation; D002478:Cells, Cultured; D019744:Chemokines, C; D003424:Crohn Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003713:Dendritic Cells / Q000378:metabolism; D006801:Humans; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D009000:Monocytes / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics; D043562:Receptors, G-Protein-Coupled; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology*; D014018:Tissue Distribution
D019744:Chemokines, C; D008222:Lymphokines; D008565:Membrane Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D012795:Sialoglycoproteins; C092390:XCL1 protein, human; C091671:XCR1 protein, human; C018997:lymphotactin