Redistribution of CD73 Expression on CD4+T Subpopulations in Systemic Lupus Erythematosus and Its Association With Disease Activity

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder driven by aberrant immune responses, predominately CD4 + T cells dysfunction. CD73, an ecto-5'-nucleotidase mediating adenosine signalling, is essential for immune regulation. Herein, we investigated CD73 expression across CD4 + T subpopulations and further explored their potential impacts on the activation and function of CD4 + T subsets, together with their associations with disease activity and clinical features of SLE. A total of 134 SLE patients, 84 disease controls antiphospholipid syndrome (APS), and 61 healthy controls (HCs) were recruited. Flow cytometry was used to profile CD73 expression across circulating CD4 + T subsets. Disease activity was assessed by SLEDAI-2 K score. We identified a subset-specific distribution pattern of CD73 expression in SLE compared with HCs, characterized by increased CD73 expression in Th1 and Th17 cells and reduced expression in Th2, Tregs, Tfh and Tfr cells. Meanwhile, significant elevated CD73-expressing Th1/Th2 ratios and obviously reduced CD73-expressing Tfh/Tfr ratios in SLE were observed. CD73-expressing Th1 cells exhibited enhanced activation phenotype manifested as elevated expression of CD25, ICOS, PD-1, and secretion of IFN-γ. Positive correlation was observed between CD73-expressing Th1 cells and CD25 expression within Th1 cells. In addition, CD73-expressing Tph cells displayed reduced secretion of IFN-γ and IL-21, and positive association was found between CD73 expression and IL-21 secretion within Tph cells. Importantly, frequencies of CD73-expressing Th1, Th2 and Tph cells were significantly reduced in active disease group relative to inactive group, and negatively correlated with SLEDAI-2 K scores, and CD73-expressing Th1 cells displayed moderate discriminatory capacity (AUC = 0.671) to differentiate active and inactive SLE. Furthermore, SLE patients with lupus nephritis showed decreased CD73-expressing Th1 cells and Tph cells, and Tph cells was diminished in patients with thrombocytopenia. These findings highlighted CD73 as a potential marker of immune dysregulation, which may be associated with the activation- and function-related cellular phenotypes. Aberrant CD73 expression may potentially be associated with disease activity and clinical manifestations of SLE patients.