Expression and function of the C-class chemokine lymphotactin (XCL1) in Wegener's granulomatosis.
OBJECTIVE
In Wegener's granulomatosis (WG), vasculitic lesions are characterized by prominent infiltration of polymorphonuclear neutrophils (PMN) and T cells, but underlying pathogenic mechanisms remain to be defined. We analyzed the expression and functional role of the C-class chemokine lymphotactin, XCL1, in WG.


METHODS
Sera and peripheral blood mononuclear cells (PBMC) were obtained from 16 patients with WG and healthy controls. Serum XCL1 concentrations were measured by ELISA. PBMC were subjected to flow cytometry for activation markers and immunophenotype of XCL1+ T cells. Renal biopsies were analyzed by double-label immunohistochemistry. In vitro stimulation of PMN with XCL1 was performed to study its function.


RESULTS
Flow cytometry demonstrated coexpression of the activation markers CD25, CD69, and HLA-DR in a significantly higher proportion of T cells in WG patients in comparison to controls. XCL1 was found to be mainly expressed in CD4+CD28- T cells in WG patients. In renal biopsies, the presence of XCL1 was only detected within interstitial CD4+ and CD8+ T cells. Functional studies demonstrated a significant enhancement of IL-8 production in isolated PMN after in vitro stimulation with XCL1. There were no significant differences in XCL1 serum concentrations between WG patients and controls (p = 0.88).


CONCLUSIONS
Our data indicated increased expression of XCL1 in CD4+ and CD8+ T cells in WG. Considering its function as a lymphocyte-specific chemoattractant, XCL1 might be a key modulator of T cell recruitment in WG. Functional studies further suggest that XCL1 may support vascular inflammation by induction of release of interleukin 8 in PMN.
Department of Nephrology and Rheumatology, University of Göttingen, Göttingen, Germany. sblasch@gwdg.de
Sabine
S
Blaschke
Philip
P
Brandt
Johannes T
JT
Wessels
Gerhard A
GA
Müller
D000328:Adult; D015703:Antigens, CD / Q000097:blood / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000097:blood / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019744:Chemokines, C / Q000097:blood* / Q000235:genetics / Q000276:immunology*; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000097:blood* / Q000276:immunology* / Q000473:pathology; D006684:HLA-DR Antigens / Q000097:blood / Q000276:immunology; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood / Q000276:immunology; D007668:Kidney / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D037181:Lectins, C-Type; D008297:Male; D008875:Middle Aged; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015415:Biomarkers; D019744:Chemokines, C; D006684:HLA-DR Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D000099192:CD69 Antigens; C508017:IL2RA protein, human; C092390:XCL1 protein, human