Chemokine receptor CCR7 is expressed in muscle fibers in juvenile dermatomyositis Carlo Minetti a, * , Marco Gattorno b , Silvia Repetto a , Andrea Gregorio b , Marina Pedemonte a , Stefania Assereto a , Federico Zara a , Claudio Bruno a , Alberto Martini b a Neuromuscular Disease Unit, University of Genova and G. Gaslini Institute, Genoa, Italy b II Division of Pediatrics, University of Genova and G. Gaslini Institute, Genoa, Italy Received 16 May 2005 Available online 6 June 2005 Abstract To better elucidate the pathogenesis of lymphocyte recruitment of memory CD4 + T cells in inflammatory myopathies, we studied the expression of CCR5 and CCR7 on CD4 memory T cells in muscle tissue from 11 patients with juvenile dermatomyositis, six adult patients with polymyositis, two patients with Duchenne muscular dystrophy, and two patients with spinal muscular atrophy. A prevalent infiltration of CCR5 + effector CD4 T memory cells is observed in inflammatory myopathies. Moreover, we found a strong expression of CCR7 in perifascicular atrophic and in degenerating/regenerating muscle fibers in juvenile dermatomyositis (JDM) but not in fibers from adult polymyositis and Duchenne muscular dystrophy. The selective expression of CCR7 in JDM may open new perspectives in the understanding of the pathogenesis of inflammatory myopathies, offering a new tool for the dif- ferential diagnosis of these disorders. Ó 2005 Elsevier Inc. All rights reserved. Keywords: Juvenile dermatomyositis; Polymyositis; Chemokines; Cytokines; CCR5; CCR7 Juvenile dermatomyositis (JDM) is an acquired inflammatory disease of unknown etiology that primar- ily affects skeletal muscle and skin. The pathogenesis of JDM is unclear, although immunological mechanisms seem to play an important role [1,2]. Muscle biopsy is characterized by degeneration/regeneration of muscle fi- bers, often revealing a perifascicular atrophy, and by mononuclear cell infiltrates, mainly composed by imma- ture dendritic cells, monocytes, and CD4 + and CD8 + lymphocytes with a prevalent memory phenotype [3,4]. To characterize the cellular infiltrates in idiopathic inflammatory myopathies, different cytokines and che- mokines have been studied [5]. In particular, CC chemo- kine receptor 5 (CCR5) was found to be expressed in the infiltrating monocytes–macrophages and lymphocytes in muscle tissue from patients with myositis [6–8]. CC chemokine receptor 7 (CCR7) has been identified as a modulator of T lymphocytes and dendritic cell traf- ficking. Moreover, CCR7 also represents an important marker of memory T-cell differentiation. In fact, it has been proposed that CCR7 + memory T cells represent a pool of ‘‘central’’ memory T cells homing to lymph nodes, where they undergo further differentiation into CCR7 À memory T cells, that migrate to the peripheral tissues to perform their effector functions [9]. Notably, CCR5 is typically highly expressed on effector memory T cells and its respective ligands (CCL4 and CCL5) are abundantly present in inflamed tissues [10]. However, CCR7 positive T lymphocytes have been also detected in inflammatory peripheral tissues, espe- cially in those inflamed tissues presenting various degrees 0006-291X/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.bbrc.2005.05.146 * Corresponding author. Fax: +39 010 3538265. E-mail address: minettic@unige.it (C. Minetti). www.elsevier.com/locate/ybbrc Biochemical and Biophysical Research Communications 333 (2005) 540–543 BBRC