Infiltrating CD8+ T cells in oral lichen planus predominantly express CCR5 and CXCR3 and carry respective chemokine ligands RANTES/CCL5 and IP-10/CXCL10 in their cytolytic granules: a potential self-recruiting mechanism.
Lichen planus is a chronic inflammatory disease of the skin and oral mucosa in which the cell-mediated cytotoxicity is regarded as a major mechanism of pathogenesis. To understand its pathophysiology further, the present study examined the in situ expression of chemokines and chemokine receptors in oral lichen planus. Immunohistochemical analysis of 15 cases has consistently revealed that infiltrating CD4(+) and CD8(+) T cells in the submucosa predominantly expressed CCR5 and CXCR3. Furthermore, infiltrating T cells, particularly CD8(+) T cells, were positive for RANTES/CCL5 and IP-10/CXCL10, the ligands of CCR5 and CXCR3, respectively. By immunoelectron microscopy, these chemokines were localized in the cytolytic granules of CD8(+) T cells. Lesional keratinocytes also overexpressed the ligands of CXCR3, namely, MIG/CXCL9, CXCL10, and I-TAC/CXCL11. Our data suggest that the chemokines signaling via CCR5 and CXCR3, which are known to be selectively expressed by type 1 T cells, are predominantly involved in T-cell infiltration of oral lichen planus. Furthermore, the presence of CCL5 and CXCL10 in the cytolytic granules of tissue-infiltrating CD8(+) T cells expressing CCR5 and CXCR3 reveals a potential self-recruiting mechanism involving activated effector cytotoxic T cells.
Iijima
Wakana
W
Division of Oral Diagnosis and Radiology, Tohoku University Graduate School of Dentistry, Sendai, Japan. wakana@mips.ne.jp
Ohtani
Haruo
H
Nakayama
Takashi
T
Sugawara
Yumiko
Y
Sato
Eiichi
E
Nagura
Hiroshi
H
Yoshie
Osamu
O
Sasano
Takashi
T
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000648:ultrastructure; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism*; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017676:Lichen Planus, Oral / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D009061:Mouth Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D054398:Receptors, CCR4; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism*; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*
C515354:CCR4 protein, human; C515187:CXCR3 protein, human; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D008024:Ligands; D054398:Receptors, CCR4; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine