title: CXCL13 is highly produced by Sézary cells and enhances their migratory ability via a synergistic mechanism involving CCL19 and CCL21 chemokines.
abstract: Chemokine and chemokine receptors expressed by normal and neoplastic lymphocytes play a key role in cell recruitment into skin and lymph nodes. The aim of this study was to get further insights into the role of chemokines in pathogenesis and progression of cutaneous T-cell lymphoma (CTCL) with particular regard to Sézary Syndrome (SS), a CTCL variant with blood involvement. Here, we show that functional CXCL13 homeostatic chemokine is strongly up-regulated in SS cells, well-detectable in skin lesions and lymph nodes, and measurable at high concentration in plasma of SS patients, at different levels during disease progression. Furthermore, we show that the addition of CXCL13 to CCL19 or to CCL21, the selective CCR7 agonists responsible for lymph node homing, strongly enhances the migration of CCR7+ SS cells. We also show that neutralization of the CCR7 receptor strongly impairs CCL19/21-induced chemotaxis of SS cells both in the absence or presence of CXCL13. Additional experiments performed to investigate the survival, adhesion, and metalloproteases secretion indicate that CXCL13 combined with CCL19 and CCL21 mainly affects the chemotaxis of SS cells. Our findings suggest that this newly described CXCL13 expression in SS represents a new pathogenetic mechanism of diagnostic significance.
authors.affiliation: Istituto Dermopatico dell'Immacolata, Laboratorio di Oncologia Molecolare, III Divisione Dermatologica, Rome, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Picchio
authors.forename: Enrico
authors.initials: E
authors.lastname: Scala
authors.forename: Debora
authors.initials: D
authors.lastname: Pomponi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Caprini
authors.forename: Marina
authors.initials: M
authors.lastname: Frontani
authors.forename: Irene
authors.initials: I
authors.lastname: Angelucci
authors.forename: Antonella
authors.initials: A
authors.lastname: Mangoni
authors.forename: Cristina
authors.initials: C
authors.lastname: Lazzeri
authors.forename: Marie
authors.initials: M
authors.lastname: Perez
authors.forename: Daniele
authors.initials: D
authors.lastname: Remotti
authors.forename: Emanuela
authors.initials: E
authors.lastname: Bonoldi
authors.forename: Roberto
authors.initials: R
authors.lastname: Benucci
authors.forename: Giannandrea
authors.initials: G
authors.lastname: Baliva
authors.forename: Giuseppe Alfonso
authors.initials: GA
authors.lastname: Lombardo
authors.forename: Monica
authors.initials: M
authors.lastname: Napolitano
authors.forename: Giandomenico
authors.initials: G
authors.lastname: Russo
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Narducci