CXCL13 is highly produced by Sézary cells and enhances their migratory ability via a synergistic mechanism involving CCL19 and CCL21 chemokines.
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.
Picchio
Maria Cristina
MC
Istituto Dermopatico dell'Immacolata, Laboratorio di Oncologia Molecolare, III Divisione Dermatologica, Rome, Italy.
Scala
Enrico
E
Pomponi
Debora
D
Caprini
Elisabetta
E
Frontani
Marina
M
Angelucci
Irene
I
Mangoni
Antonella
A
Lazzeri
Cristina
C
Perez
Marie
M
Remotti
Daniele
D
Bonoldi
Emanuela
E
Benucci
Roberto
R
Baliva
Giannandrea
G
Lombardo
Giuseppe Alfonso
GA
Napolitano
Monica
M
Russo
Giandomenico
G
Narducci
Maria Grazia
MG