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dc.contributor.advisorLu, Theresa
dc.contributor.authorShipman, William
dc.date.accessioned2019-03-26T19:13:03Z
dc.date.available2019-03-27T06:00:53Z
dc.date.issued2018
dc.identifier.urihttps://hdl.handle.net/1813/64781
dc.description.abstractPhotosensitivity, or skin sensitivity to ultraviolet radiation (UVR), is a feature of lupus erythematosus (LE) and other autoimmune and dermatologic conditions, but the mechanistic underpinnings are poorly understood. Here, we identify a Langerhans cell (LC)-keratinocyte axis that limits UVR-induced keratinocyte apoptosis and skin injury via keratinocyte epidermal growth factor receptor (EGFR) stimulation. We show that the absence of LCs in Langerin-DTA mice leads to photosensitivity and that, in vitro, mouse and human LCs can directly protect keratinocytes from UVR-induced apoptosis. LCs express EGFR ligands and ADAM17, the metalloprotease that cleaves and activates EGFR ligands. Deletion of ADAM17 from LCs leads to photosensitivity and UVR induces LC ADAM17 activation and generation of soluble active EGFR ligands, suggesting that LCs protect by providing activated EGFR ligands to keratinocytes. Photosensitive systemic LE (SLE) models and human SLE skin show reduced epidermal EGFR phosphorylation and LC defects, and topical EGFR ligand reduces photosensitivity. Together, our data establish a direct tissue-protective function for LCs, reveal a mechanistic basis for photosensitivity, and suggest EGFR stimulation as a treatment for photosensitivity in LE and potentially other autoimmune and dermatologic conditions.
dc.language.isoen_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectLangerhans cells
dc.subjectLupus
dc.subjectPhotosensitivity
dc.subjectUVR apoptosis
dc.titleA Protective Langerhans Cell-Keratinocyte Axis That Is Dysfunctional In Photosensitivity
dc.typedissertation or thesis
thesis.degree.disciplineImmunology & Microbial Pathogenesis
thesis.degree.grantorWeill Cornell Graduate School of Medical Sciences
thesis.degree.levelDoctor of Philosophy


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