Coincident expression of the chemokine receptors CCR6 and CCR7 by pathologic Langerhans cells in Langerhans cell histiocytosis.
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.
Fleming
Mark D
MD
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Pinkus
Jack L
JL
Fournier
Marcia V
MV
Alexander
Sarah W
SW
Tam
Carmen
C
Loda
Massimo
M
Sallan
Stephen E
SE
Nichols
Kim E
KE
Carpentieri
David F
DF
Pinkus
Geraldine S
GS
Rollins
Barrett J
BJ
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
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