Article ; Online: Co-culture of healthy human keratinocytes and T-cells promotes keratinocyte chemokine production and RORγt-positive IL-17 producing T-cell populations.
Journal of dermatological science
2013 Volume 69, Issue 1, Page(s) 44–53
Abstract: Background: Both keratinocytes and T-cells are crucial players in cutaneous immune responses. We hypothesized that direct interactions between keratinocytes and T-cell subsets could shape the nature or strength of the local immune response.: Objective! ...
| Abstract | Background: Both keratinocytes and T-cells are crucial players in cutaneous immune responses. We hypothesized that direct interactions between keratinocytes and T-cell subsets could shape the nature or strength of the local immune response. Objective: We investigated direct interactions between keratinocytes and T-cell subsets, focused on keratinocyte chemokine production and T-cell phenotype and cytokine production. Methods: A newly developed in vitro serum free co-culture model using primary keratinocytes and T-cells subsets from healthy human donors was used. Keratinocyte chemokine production was analyzed with luminex, T-cell phenotype and cytokine production were analyzed with flow cytometry. Results: Our data show that upon co-culture with CD4(pos) or CD8(pos) T-cells primary human keratinocytes increased production of functionally active chemokines CCL2, CCL20 and CXCL10 and that regulatory T-cells did not regulate keratinocyte chemokine production. Next to that, we found that keratinocytes skewed CD4(pos) and CD8(pos) T-cell populations toward an IL-17(pos) CCR6(pos) RORγt(pos) phenotype in a cell-cell contact independent manner, and that Treg were able to decrease the absolute number of IL-17 producing T-cells in keratinocyte/T-cell co-cultures. Correspondingly, freshly isolated skin-derived T-cell populations contained relatively high percentages of IL-17(pos) cells. Conclusion: We provide evidence that keratinocyte/T-cell communication may regulate leukocyte influx in the skin, and that keratinocytes enrich T-cell populations for Th17/Tc17 cells. Accumulation of Th17/Tc17 cells, but not chemokine production, appears under the control of regulatory T-cells. Dysregulation of these processes may well contribute to the pathophysiology of inflammatory skin diseases. |
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| MeSH term(s) | Analysis of Variance ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cell Communication ; Cells, Cultured ; Chemokine CCL2/metabolism ; Chemokine CCL20/metabolism ; Chemokine CXCL10/metabolism ; Coculture Techniques ; Fibroblasts/immunology ; Humans ; Keratinocytes/immunology ; Keratinocytes/metabolism ; Nuclear Receptor Subfamily 1, Group F, Member 3 ; Phenotype ; Skin/immunology ; T-Lymphocytes, Regulatory/immunology ; Th17 Cells/immunology ; Th17 Cells/metabolism |
| Chemical Substances | Chemokine CCL2 ; Chemokine CCL20 ; Chemokine CXCL10 ; Nuclear Receptor Subfamily 1, Group F, Member 3 |
| Language | English |
| Publishing date | 2013-01 |
| Publishing country | Netherlands |
| Document type | Journal Article |
| ZDB-ID | 1024446-3 |
| ISSN | 1873-569X ; 0923-1811 |
| ISSN (online) | 1873-569X |
| ISSN | 0923-1811 |
| DOI | 10.1016/j.jdermsci.2012.10.004 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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