Type III Interferon in Autoimmune Disease

Type I interferon production from nucleic acid-sensing pathways drives systemic lupus erythematosus pathogenesis according to current dogma. However, type III interferons (IFN-λ) can stimulate a similar gene expression profile utilizing a unique receptor. IFN-λ is detected in the blood, kidneys, and skin of lupus patients. The contribution of IFN-λ to lupus and lupus nephritis pathogenesis is currently unknown. The objective of this project is to identify which innate interferon pathways are dominant in the human renal microenvironment of lupus nephritis.

Immunohistochemistry and laser microdissection of patient renal biopsies will be used to assess in situ protein and RNA expression of innate interferons and their gene signatures. One working hypothesis is that nucleic acid sensors, IFN-α, and IFN-λ stimulate innate interferon production in human renal tubule epithelial cells to promote lupus pathogenesis.

Long-term goals include establishing the functional role of IFN-λ in lupus and the renal microenvironment including its contribution to renal fibrosis and end-stage kidney disease. Understanding how innate interferon pathways interconnect will allow for their therapeutic calibration for improved lupus patient outcome as well as in other autoimmune and viral diseases.

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