Langerhans cells regulate cutaneous injury by licensing CD8 effector cells recruited to the skin
| Autor: | Frederic Geissmann, Ronjon Chakraverty, Thomas Conlan, Terry K. Means, Céline Trouillet, Farnaz Fallah-Arani, Hugh D. Goold, Barry Flutter, Laurent Chorro, Clare L. Bennett |
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| Rok vydání: | 2011 |
| Předmět: |
Cytotoxicity
Immunologic Graft vs Host Disease Cell Communication Biochemistry Granzymes TNF-Related Apoptosis-Inducing Ligand Mice 0302 clinical medicine Cells Cultured Mice Inbred BALB C 0303 health sciences education.field_of_study Toll-like receptor Imiquimod integumentary system biology Effector Toll-Like Receptors hemic and immune systems Hematology Cell biology medicine.anatomical_structure Aminoquinolines Langerhans cell Immunology Population Mice Transgenic chemical and pharmacologic phenomena Interferon-gamma 03 medical and health sciences Immune system medicine Animals RNA Messenger Antigen-presenting cell education Immunobiology 030304 developmental biology Chimera Tumor Necrosis Factor-alpha Cell Biology Mice Inbred C57BL Gene Expression Regulation Granzyme Langerhans Cells biology.protein Epidermis T-Lymphocytes Cytotoxic 030215 immunology Homing (hematopoietic) |
| Zdroj: | Blood |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Langerhans cells (LCs) are a distinct population of dendritic cells that form a contiguous network in the epidermis of the skin. Although LCs possess many of the properties of highly proficient dendritic cells, recent studies have indicated that they are not necessary to initiate cutaneous immunity. In this study, we used a tractable model of cutaneous GVHD, induced by topical application of a Toll-like receptor agonist, to explore the role of LCs in the development of tissue injury. By adapting this model to permit inducible and selective depletion of host LCs, we found that GVHD was significantly reduced when LCs were absent. However, LCs were not required either for CD8 T-cell activation within the draining lymph node or subsequent homing of effector cells to the epidermis. Instead, we found that LCs were necessary for inducing transcription of IFN-γ and other key effector molecules by donor CD8 cells in the epidermis, indicating that they license CD8 cells to induce epithelial injury. These data demonstrate a novel regulatory role for epidermal LCs during the effector phase of an inflammatory immune response in the skin. |
| Databáze: | OpenAIRE |
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