CXCL13, CCL21, and CXCL12 expression in salivary glands of patients with Sjogren's syndrome and MALT lymphoma: association with reactive and malignant areas of lymphoid organization.
The chemokines (CKs) CXCL13, CCL21, and CXCL12 are known to play differential roles in the organization of the lymphoid tissues and the development of lymphoid malignancies. We investigated the expression of these CKs and their receptors in the salivary glands of Sjogren's syndrome patients with lymphoepithelial lesions (lymphoepithelial sialadenitis or LESA) and in MALT lymphoma to understand their involvement in salivary gland lymphomagenesis. We demonstrate that within salivary glands with LESA and MALT lymphoma the lymphoid CKs CXCL13 and CCL21 are selectively associated with areas of reactive lymphoid proliferation, whereas no significant expression of these molecules was detected in the malignant lymphoid aggregate. Conversely, CXCL12 was observed predominantly in infiltrated ducts and malignant B cells. Accordingly, CXCL13 and CCL21 transcript levels were significantly increased in LESA samples while CXCL12 levels were increased in MALT lymphoma and isolated tumor cells. Low levels of CK receptors were detected on lymphoma-extracted lymphocytes, suggesting down-regulation in the abundance of ligands. Our findings suggest that in salivary gland MALT lymphoma the lymphoid CKs CXCL13 and CCL21 are directly implicated in the organization of ectopic reactive lymphoid tissue, whereas CXCL12 is associated with the infiltrated epithelium and malignant B cell component and is possibly involved in the regulation of malignant B cell survival.
Barone
Francesca
F
Divisione di Reumatologia Dipartimento di Clinica e Terapia Applicata, Università La Sapienza Roma, Rome, Italy.
Bombardieri
Michele
M
Rosado
Manuela Maria
MM
Morgan
Peter Roger
PR
Challacombe
Stephen J
SJ
De Vita
Salvatore
S
Carsetti
Rita
R
Spencer
Jo
J
Valesini
Guido
G
Pitzalis
Costantino
C
D000328:Adult; D000368:Aged; D054421:Chemokine CCL21 / Q000235:genetics / Q000378:metabolism*; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D054382:Chemokine CXCL13 / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008221:Lymphoid Tissue / Q000378:metabolism* / Q000473:pathology; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012469:Salivary Glands / Q000378:metabolism*; D012859:Sjogren's Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D014158:Transcription, Genetic
C110663:CXCL13 protein, human; D054421:Chemokine CCL21; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13