In vivo tracking of skin-derived immune cells in murine models of Psoriasis using Dendra2 photoconversion
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Abstract
Psoriasis is a chronic, systemic and inflammatory skin disease with comorbidities including cardiovascular disease, inflammatory bowel disease and non-alcoholic fatty liver disease. However, whether skin-derived immune cells contribute directly to systemic pathology remains unclear. In this study, I established and validated Dendra2-based photoconversion as a robust in vivo platform for quantitative tracking of skin-derived immune cell trafficking across lymphoid and non-lymphoid organs in murine psoriasis models, providing direct mechanistic insight into how psoriatic inflammation influences systemic immunity.
The method was first optimized in the acute IMQ-induced psoriasis model. Photoconversion of inflamed skin was feasible, non-invasive and did not alter disease progression. The red Dendra2 signal remained stable during tissue processing and flow cytometry, enabling sensitive detection of skin-derived immune cells. Analyses revealed that immune cells from the skin migrate primarily to draining lymph nodes and the spleen, with no detectable trafficking to distant organs such as the aorta or bone marrow.
Application of the method to the chronic K14-IL-17Aind/+ model, which mimics sustained IL-17A-driven systemic inflammation originating from the skin, confirmed efficient labeling of immune cells in the skin. Dendra2-red+ cells were detectable in lymphoid organs and, at extremely low frequency, in the liver. Migratory populations in lymphoid organs were predominantly CD11b+ myeloid cells and T cells, whose proportions were largely unchanged during psoriatic inflammation. Even under chronic systemic inflammation, migration to distant organs, including the aorta, colon and liver, remained absent or minimal, demonstrating that organ inflammation is driven primarily by systemic cytokine-mediated immune activation and bone marrow-derived myeloid cell mobilization, rather than direct skin-to-organ immune cell trafficking.
Overall, this work establishes Dendra2 photoconversion as a powerful and reliable tool for in vivo tracking of skin-derived immune cells and provides strong evidence that systemic IL-17A-driven inflammation, rather than immune cell egress from the skin, drives vascular, intestinal and hepatic pathology in psoriasis. These findings highlight the importance of targeting systemic IL-17A-driven inflammation to prevent psoriasis-associated comorbidities and establish a versatile platform for studying organ-organ immune cell crosstalk in chronic inflammatory disease.