The multiple roles of GM-CSF in autoimmune and autoinflammatory uveitis

Uveitis is an inflammatory disorder of the eye that causes severe vision loss. In autoimmune and autoinflammatory diseases, such as multiple sclerosis (MS) and rheumatoid arthritis (RA), granulocyte-macrophage colony-stimulating factor (GM-CSF) has been indicated to play a significant pathogenic role that depends on cellular immune responses. Emerging evidence from both experimental models and clinical studies of uveitis suggests that GM-CSF plays a far more complex role than its originally described function as a hematopoietic growth factor that promotes the differentiation of granulocytes and macrophages from progenitor cells. This review presents an updated perspective on the central role of GM-CSF in the pathogenesis of autoimmune and autoinflammatory uveitis, with particular emphasis on its dual role in initiating and modulating inflammatory responses. GM-CSF functions as a critical molecular bridge between innate and adaptive immunity, uniquely positioned to coordinate immune cell crosstalk and respond to a wide range of inflammatory stimuli. Its capacity to both sense and transmit inflammatory signals, particularly within the innate immune system, underscores its multifaceted effector functions. Here, we summarize current evidence on GM-CSF's sources, responsive cells, and its complex involvement, both pro-inflammatory and potentially regulatory, in peripheral blood and aqueous humor during uveitis. Furthermore, we discuss the implications of GM-CSF in other inflammatory/autoimmune diseases. We also delineate the research progress on targeting GM-CSF in therapeutics for uveitis and other related conditions, with the expectation of providing new insights into their treatments.