Role of CD4+ T cell-derived cytokines in the pathogenesis of uveitis

Abstract

Uveitis refers to a diverse group of inflammatory diseases that affecting the uveal tract, comprising the iris, ciliary body, and choroid, with potential repercussions ranging from visual impairment to blindness. The role of autoimmunity in uveitis etiology is complex and still under investigation. CD4⁺ T cells intricately regulate immune responses in uveitis through their diverse subtypes: Th1, Th2, Th17, Treg (T regulatory), and Tfh (follicular T helper) cells. Each T cell subtype secretes specific cytokines with either pathogenic or protective implications in uveitis. Th1 cells, characterized by IFN-γ secretion and T-bet expression, drive type 1 immune responses against intracellular pathogens. Conversely, Th2 cells, which produce interleukin (IL)-4, IL-5, and IL-13 and express the transcription factor GATA3, mediate type 2 immune responses to larger extracellular threats like helminths. Th17 cells, generating IL-17 and IL-22 and controlled by RORγt, engage in type 3 immune responses against select pathogens. Tfh cells, releasing IL-21 and governed by Bcl6, aid B cell antibody production. Conversely, Tregs, identified by Foxp3, exert regulatory functions in immune homeostasis. This review delves into the roles of CD4⁺ T cell-derived cytokines in uveitis, emphasizing their intricate involvement in disease progression and resolution. Insight into these mechanisms might guide therapeutic approaches targeting CD4⁺ T cell responses in uveitis management.

Keywords: Autoimmunity; CD4+ T Cells; Cytokines; Pathogenesis; Uveitis.

Fig. 1

Probable primary causes of uveitis, highlighting the multifactorial nature of this inflammatory eye condition. Created with BioRender.com

Fig. 2

CD4⁺ T cells differentiate into various subsets based on the cytokine environment during activation. Th1 cells, induced by IL-12 and IL-18, produce IFN-γ to activate macrophages against M. tuberculosis. Th2 cells release IL-4 to stimulate macrophages against parasites, though IL-4’s source is unclear. Tfh cells secrete Th1 and Th2 cytokines, including IL-21, and are crucial for B cell activation. Th17 cells produce IL-17 and IL-22 with IL-6 and TGF-β, recruiting neutrophils and defending against extracellular pathogens. Activated T cells can also become Tregs with TGF-β and/or retinoic acid, regulating immune responses and preventing excessive inflammation. Created with BioRender.com