The Relationship between Type I Interferon and Group 2 Innate Lymphoid Cells in Systemic Lupus Erythematosus
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Date
2019-05
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The Ohio State University
Abstract
Systemic lupus erythematous (SLE) is an autoimmune disease that affects multiple organ systems. Type I interferons (IFN) stimulate inflammatory responses to infection and are upregulated in SLE. Group 2 innate lymphoid cells (ILC2s) are immune cells that are protective against infections and participate in wound healing; however, the relationship between ILC2s and SLE is fairly unknown. Nevertheless, there has been some research suggesting that type I IFN inhibits ILC2s. Therefore, we hypothesize that cutaneous ILC2s are inhibited by type I IFNs in SLE patients with skin rashes; this subset of patients is defined as having cutaneous lupus erythematosus (CLE). Patients with CLE and normal controls donated two 6 mm skin punch biopsies and peripheral whole blood. ILC2s were purified from the collected skin and analyzed by flow cytometry. Imiquimod is a cream that induces lupus-like skin lesions when topically applied. Imiquimod and control cream were applied to two separate cohorts of mice for 4 weeks. To monitor disease, weight was recorded along with urine and blood. At the end of the project, RNA scope and immunohistochemistry (IHC) were used to characterize various immune mediators. The human patients with cutaneous lupus lesions had higher levels of type I IFN-regulated genes when compared to the healthy control patients as well as a lower circulating concentration of ILC2s. The proportion of dermal ILC2s was also decreased in the lesional skin of CLE patients compared to their non-lesional skin and healthy control skin. In the imiquimod mouse model, similar results were observed. For example, we found that imiquimod-treated mice had less dermal ILC2s as well as increased type I IFN signatures when compared to control mice. Taken together, these findings suggest that elevated type I IFN signatures found in skin rashes of lupus patients may have an inhibitory effect on dermal ILC2s and on circulating ILC2s as well.
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Keywords
lupus, interferon, innate lymphoid cells, mouse model, immunology, SLE