title: Coincident expression of the chemokine receptors CCR6 and CCR7 by pathologic Langerhans cells in Langerhans cell histiocytosis.
abstract: It has been suggested that a switch in chemokine receptor expression underlies Langerhans cell migration from skin to lymphoid tissue. Activated cells are thought to down-regulate CCR6, whose ligand macrophage inflammatory protein-3 alpha (MIP-3 alpha)/CCL20 is expressed in skin, and up-regulate CCR7, whose ligands are in lymphoid tissues. In Langerhans cell histiocytosis (LCH), pathologic Langerhans cells (LCs) accumulate in several tissues, including skin, bone, and lymphoid organs. We have examined 24 LCH cases and find that pathologic LCs expressed CCR6 and CCR7 coincidentally in all cases. Furthermore, MIP-3 alpha/CCL20 is expressed by keratinocytes in involved skin and by macrophages and osteoblasts in involved bone. Expression of CCR6 by pathologic LCs may contribute to their accumulation in nonlymphoid organs such as skin and bone, whereas CCR7 expression may direct them to lymphoid tissue. Histiocytes in Rosai-Dorfman disease and hemophagocytic syndrome also coexpressed CCR6 and CCR7, suggesting that this may be a general attribute of abnormal histiocytes.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Fleming
authors.forename: Jack L
authors.initials: JL
authors.lastname: Pinkus
authors.forename: Marcia V
authors.initials: MV
authors.lastname: Fournier
authors.forename: Sarah W
authors.initials: SW
authors.lastname: Alexander
authors.forename: Carmen
authors.initials: C
authors.lastname: Tam
authors.forename: Massimo
authors.initials: M
authors.lastname: Loda
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Sallan
authors.forename: Kim E
authors.initials: KE
authors.lastname: Nichols
authors.forename: David F
authors.initials: DF
authors.lastname: Carpentieri
authors.forename: Geraldine S
authors.initials: GS
authors.lastname: Pinkus
authors.forename: Barrett J
authors.initials: BJ
authors.lastname: Rollins
mesh_terms: D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000032:analysis / Q000502:physiology; D002633:Chemotaxis; D006646:Histiocytosis, Langerhans-Cell / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000737:chemistry; D007801:Langerhans Cells / Q000737:chemistry / Q000473:pathology*; D019402:Macrophage Inflammatory Proteins / Q000032:analysis / Q000502:physiology; D008264:Macrophages / Q000737:chemistry; D010006:Osteoblasts / Q000737:chemistry; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000502:physiology
chemical_list: C108355:CCL20 protein, human; C106311:CCR6 protein, human; C515370:CCR7 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D019707:Receptors, Chemokine