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IL-27 is an IL-12 family cytokine with immunomodulatory properties, capable of modulating inflammatory responses including autoimmunity. Although extensive studies have investigated the primary target cells of IL-27 mediating its function, the source of IL-27, especially during tissue-specific autoimmune inflammation, has not been formally investigated. The IL-27p28 subunit, also known as IL-30, was originally found to be an IL-27-specific subunit and was therefore considered a surrogate marker for IL-27 expression.