2008Journal of Cutaneous PathologyRequires access

Involvement of granzyme B and granulysin in the cytotoxic response in lichen planus

M. Ammar, M. Mokni, S Boubaker, Amel El Gaied, A. Ben Osman, Hechmi Louzir

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Abstract

BACKGROUND: Lichen planus is an inflammatory dermatosis involving either skin and/or mucosal epithelial surfaces. A cell-mediated cytotoxicity response is the main suspected mechanism of this dermatosis. Granzyme B and granulysin are components of the cytoplasmic granules of cytotoxic T lymphocytes and natural killers. They are involved in cell-mediated apoptosis. This work studies the possible implication of granzyme B and granulysin in the cell-mediated cytotoxicity response in lichen planus. METHODS: In situ expression of granzyme B and granulysin was studied by real-time reverse transcriptase polymerase chain reaction in 15 biopsies of lichen planus. The distribution and the phenotype of the inflammatory infiltrate and the expression of granzyme B were studied by immunohistochemistry in seven other biopsies of lichen planus. RESULTS: Granzyme B and granulysin mRNA expression was one to two hundred times greater than in biopsies of normal skin. Immunohistochemical study revealed that the lymphohistiocytic infiltrate consisted mainly of CD4+ and CD8+ lymphocytes. Granzyme B+ cells were observed close to apoptotic keratinocytes. CONCLUSION: Our results suggest a central role for cell-mediated cytotoxicity by the granule exocytosis pathway probably because of auto-cytotoxic T-cell clones in the pathogenesis of lichen planus.

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BACKGROUND: Lichen planus is an inflammatory dermatosis involving either skin and/or mucosal epithelial surfaces. A cell-mediated cytotoxicity response is the main suspected mechanism of this dermatosis. Granzyme B and granulysin are components of the cytoplasmic granules of cytotoxic T lymphocytes and natural killers. They are involved in cell-mediated apoptosis. This work studies the possible implication of granzyme B and granulysin in the cell-mediated cytotoxicity response in lichen planus. METHODS: In situ expression of granzyme B and granulysin was studied by real-time reverse transcriptase polymerase chain reaction in 15 biopsies of lichen planus. The distribution and the phenotype of the inflammatory infiltrate and the expression of granzyme B were studied by immunohistochemistry in seven other biopsies of lichen planus. RESULTS: Granzyme B and granulysin mRNA expression was one to two hundred times greater than in biopsies of normal skin. Immunohistochemical study revealed that the lymphohistiocytic infiltrate consisted mainly of CD4+ and CD8+ lymphocytes. Granzyme B+ cells were observed close to apoptotic keratinocytes. CONCLUSION: Our results suggest a central role for cell-mediated cytotoxicity by the granule exocytosis pathway probably because of auto-cytotoxic T-cell clones in the pathogenesis of lichen planus.

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Available abstract

BACKGROUND: Lichen planus is an inflammatory dermatosis involving either skin and/or mucosal epithelial surfaces. A cell-mediated cytotoxicity response is the main suspected mechanism of this dermatosis. Granzyme B and granulysin are components of the cytoplasmic granules of cytotoxic T lymphocytes and natural killers. They are involved in cell-mediated apoptosis. This work studies the possible implication of granzyme B and granulysin in the cell-mediated cytotoxicity response in lichen planus. METHODS: In situ expression of granzyme B and granulysin was studied by real-time reverse transcriptase polymerase chain reaction in 15 biopsies of lichen planus. The distribution and the phenotype of the inflammatory infiltrate and the expression of granzyme B were studied by immunohistochemistry in seven other biopsies of lichen planus. RESULTS: Granzyme B and granulysin mRNA expression was one to two hundred times greater than in biopsies of normal skin. Immunohistochemical study revealed that the lymphohistiocytic infiltrate consisted mainly of CD4+ and CD8+ lymphocytes. Granzyme B+ cells were observed close to apoptotic keratinocytes. CONCLUSION: Our results suggest a central role for cell-mediated cytotoxicity by the granule exocytosis pathway probably because of auto-cytotoxic T-cell clones in the pathogenesis of lichen planus.

Key concepts: Granulysin, Granzyme B, Granzyme, Granzyme A, Cytotoxic T cell, Biology, Cytotoxicity, Immunology

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