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Differential expression of CXCR3 targeting chemokines CXCL10, CXCL9, and CXCL11 in different types of skin
J Flier1, D M Boorsma, P J van Beek
1Department of Dermatology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
Abstract:
Recruitment of activated T-cells to the skin is a common feature in a wide variety of inflammatory skin diseases. As CXCR3 activating chemokines CXCL10 (IP-10), CXCL9 (Mig), and CXCL11 (IP-9/I-TAC) specifically attract activated T-cells, this study addressed the question of whether differences in the expression of these chemokines correlate with the site and cellular composition of the skin infiltrates in different types of inflammatory skin disease. Skin biopsies from lichen planus, chronic discoid lupus erythematosus, allergic patch test reactions, psoriasis, and Jessner's lymphocytic infiltration of the skin were investigated for chemokine expression using RNA in situ hybridization, and for the expression of CXCR3 using immunohistochemistry. The results showed differential expression of CXCL10, CXCL9, and CXCL11, which correlated with differences in the localization and cellular composition of the infiltrates. Whereas CXCL10 and CXCL11 were mainly expressed by basal keratinoctyes, CXCL9 mRNA expression was located predominantly in the dermal infiltrates. Correlation with immunohistochemical data suggested that macrophages and activated keratinocytes were the main producers of these chemokines. CXCR3 was expressed by a majority of both CD4+ and CD8+ infiltrating T-cells, suggesting a functional interaction between locally produced chemokines and CXCR3-expressing T-cells. In conclusion, these findings indicate that these CXCR3 activating chemokines play a significant role in the recruitment and maintenance of T-cell infiltrates in the inflammatory skin diseases studied.
Insights
Chemokines CXCL10, CXCL9, and CXCL11 guide T-cells in skin inflammation. Their varied expression in diseases like psoriasis correlates with T-cell infiltration sites and types, impacting disease.
Area of Science:
- Immunology
- Dermatology
- Molecular Biology
Background:
- Activated T-cell recruitment to skin is characteristic of many inflammatory skin diseases.
- Chemokines CXCL10 (IP-10), CXCL9 (Mig), and CXCL11 (IP-9/I-TAC) are known to attract activated T-cells.
Purpose of the Study:
- To investigate if chemokine expression differences correlate with skin infiltrate localization and cellular composition in various inflammatory skin diseases.
- To understand the role of specific chemokines in T-cell recruitment in skin conditions.
Main Methods:
- Analysis of skin biopsies from patients with lichen planus, chronic discoid lupus erythematosus, allergic patch tests, psoriasis, and Jessner's lymphocytic infiltration.
- RNA in situ hybridization to detect chemokine expression (CXCL10, CXCL9, CXCL11).
- Immunohistochemistry to assess CXCR3 expression on infiltrating T-cells.
Main Results:
- Differential expression patterns of CXCL10, CXCL9, and CXCL11 were observed across the studied skin diseases.
- CXCL10 and CXCL11 were primarily expressed by basal keratinocytes, while CXCL9 mRNA was found in dermal infiltrates.
- Macrophages and activated keratinocytes were identified as major chemokine producers.
- CXCR3 was expressed on most CD4+ and CD8+ infiltrating T-cells, indicating functional chemokine-T-cell interaction.
Conclusions:
- The findings suggest that CXCL10, CXCL9, and CXCL11 play a crucial role in the recruitment and persistence of T-cell infiltrates in inflammatory skin diseases.
- Chemokine expression patterns are linked to the specific characteristics of skin infiltrates in different inflammatory conditions.
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