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* Divisione di Reumatologia Dipartimento di Clinica e Terapia Applicata, Università La Sapienza Roma, Rome, Italy;
Research Center Ospedale Pediatrico Bambino Gesù, Rome, Italy;
Clinica di Reumatologia, Department of Experimental and Clinical Pathology and Medicine, Università di Udine, Azienda Ospedaliero-Universitaria, Udine, Italy;
Centre for Experimental Medicine and Rheumatology, John Vane Science Centre, William Harvey Research Institute, St. Bartholomew’s and Royal London School of Medicine, London, United Kingdom; and
¶ Department of Oral Pathology and Oral Medicine at Guy’s, St. Thomas and King’s College Dental Institute and
|| Department of Immunobiology, Division of Immunology, Infection and Inflammatory Diseases at Guy’s, St. Thomas and King’s College School of Medicine, King’s College, London, United Kingdom
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by the educational grants from the Italian Society of Rheumatology and the British Sjögren’s syndrome association and from the European Commission Directorate of Research FP-6: Innovative Chemokine-based Therapeutic Strategies for Autoimmunity and Chronic Inflammation. M.B. is recipient of a Clinical Research Fellowship from the Arthritis Research Campaign (grant reference 17132).
2 F.B. and M.B. contributed equally to this work.
3 Current address: Department of Immunobiology, Division of Immunology, Infection, and Inflammatory Diseases at Guy’s, St. Thomas and King’s College, School of Medicine, Guy’s Campus, London SE1 9RT, U.K.
4 Address correspondence and reprint requests to Dr. C. Pitzalis, Centre for Experimental Medicine and Rheumatology, Second Floor, John Vane Science Centre, William Harvey Research Institute, St. Bartholomew’s and Royal London School of Medicine, Charterhouse Square, London EC1M 6BQ, U.K. E-mail address: c.pitzalis{at}qmul.ac.uk
5 Abbreviations used in this paper: CK, chemokine; AID, activation-induced cytidine deaminase; GC, germinal center; FDC, follicular dendritic cell; HEV, high endothelial venue; LESA, lymphoepithelial sialoadenitis; MALT-L, MALT lymphoma; mSG, minor (labial) salivary gland; MSG, major salivary gland; MZ, marginal zone; PB, peripheral blood; SS, Sjogren’s syndrome; PNAd, peripheral node addressin; VFA, volume fraction area; MZ, marginal zone.
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