Homeostatic & Inflammatory Chemokine Receptors in the Synovial Infiltrate of Patients w/JIA

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RELATIONSHIPS AMONG HOMEOSTATIC AND INFLAMMATORY CHEMOKINE RECEPTORS IN

THE SYNOVIAL INFILTRATE OF PATIENTS WITH JUVENILE IDIOPATHIC ARTHRITIS

Category: 11 Pediatric rheumatology – pathogenesis and genetics

Marco Gattorno, Francesca Ferlito, Gregorio, Ignazia Prigione,

Fabio Morandi, Angelo Ravelli, Enrico Felici, Elena Sala, Vito Pistoia,

Alberto i. " G. Gaslini " Institute, Genova, Italy

Presentation Number: 872 Poster Board Number: 252

Purpose: to investigate the phenotypical and functional characteristics

of CCR7+ and CCR7- memory T cells infiltrating the synovial environment

in patients with JIA. Moreover, the synovial distribution of this

receptor for homeostatic chemokines has been compared with that of other

chemokine receptors, namely CXCR3 and CCR5, specific for

pro-inflammatory chemokines commonly found to be over-expressed in the

inflamed synovium

Methods: freshly isolated peripheral blood (PB) and synovial fluid (SF)

memory T cells from 25 JIA patients were studied for the expression of

CCR7, CCR5, CXCR3 and IFN-?, by flow-cytometry. Chemotactic activity of

CD4 and CD8 memory T cells from SF of 8 JIA patients to inflammatory

(CXCL11 and CCL3) and homeostatic (CCL19, CCL21) chemokines was also

evaluated. Synovial tissue (ST) from 6 JIA patients were also evaluated

by for the expression of CCR7, CXCR3, CCR5 and CCL21.

Results: an enrichment of CCR7- memory CD4 T cells was demonstrated in

SF vs paired blood from JIA patients. Nonetheless, a consistent number

of SF memory T still displayed a CCR7+ phenotype. SF CCR7- memory T

cells were enriched for CCR5+ and IFN-?[[unsupported Character -

& #61483;]] cells, whereas CCR7+ memory T cells showed a higher

co-expression of CXCR3. Expression of CCL21 was detected both in SF and

synovial membranes. SF memory T cells displayed a significant migration

to both inflammatory and homeostatic chemokines.

CCR7+ T cells were detected in the ST in either diffuse perivascular

lymphocytic infiltrates or in organized lymphoid aggregates. In ST, a

large fraction of CCR7+ cells co-expressed CXCR3, especially at the

level of lymphoid aggregates, conversely CCR5+ cells were predominantly

present at the level of lining layer and sublining zone of the

superficial subintima.

Conclusions. CCR7 may play a role in the synovial recruitment of memory

T cells in the JIA, irrespective of the pattern of lymphoid

organization. Moreover, a distinct pattern of chemokine receptors is

present in the context of ST.

Commercial Relationship: M. Gattorno, None; F. Ferlito, None; A.

Gregorio, None; I. Prigione, None; F. Morandi, None; A. Ravelli, None;

E. Felici, None; E. Sala, None; V. Pistoia, None; A. i, None.