Migration of Skin Dendritic Cells in Response to Ionizing Radiation Exposure

Department of Microbiology, University of Rochester Medical Center, Rochester, New York 14642, USA.
Radiation Research (Impact Factor: 2.91). 07/2009; 171(6):687-97. DOI: 10.1667/RR1600.1
Source: PubMed


We describe an imaging assay that monitors the migration of two unique subsets of immune dendritic cells (DC), interstitial dendritic cells (iDC) and Langerhans cells (LC), found in the dermal and epidermal layers of skin, respectively. Using this assay, we study responses of these cells to ionizing radiation. Results obtained using whole-mount histology and fluorescence microscopy suggest that ionizing radiation triggered the migration of both major histocompatibility complex (MHC) class II(+) iDC and Langerin(+) LC in a dose- and time-dependent manner. Migration appeared to be limited by local administration of recombinant IL-12, a potent immunostimulatory cytokine known to induce DNA repair. Those findings were extended to an in vivo model by injecting fluorescently conjugated anti-MHC class II antibodies intradermally into the ears of live, anesthetized mice and visualizing the DC population in the same ear before and after radiation exposure using confocal microscopy.

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    • "While the mechanism of increased DC migration to skin-draining lymph nodes after ionizing radiation remains unclear, acute radiation toxicity of the skin is associated with elevated levels of inflammatory cytokines and chemokines, including IL-1α, IL-1β, TNF-α, CCL4, CXCL10, and CCL2 [30-32]. Of the major groups of skin-derived DCs, both the epidermal LCs and the dermal DCs have been found to be depleted from the skin following local irradiation [33]. Our data identifying an increase in skin-derived DCs in the inguinal lymph nodes 24 hours following irradiation suggests that these skin DCs have indeed migrated to the draining lymph nodes, rather than dying off within the skin. "
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    • "More intriguing in respect to recent interests in mitigation rather than radioprotection is the intimate connection between inflammation and immunity, particularly through the activation and maturation of antigen-presenting cells (APC). The most powerful APC are dendritic cells and, for example, Lord and colleagues investigated the responses of epidermal (Langerhans cells) and interstitial dendritic cells to irradiation, demonstrating that there is a dose-related depletion of cutaneous dendritic cells following irradiation, with both populations sharing similar migratory kinetics following injury (Cummings et al. 2009). Furthermore, the group showed that the immunostimulatory cytokine, IL-12 (BD Biosciences, San Jose, CA, USA), mediated these effects. "
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