T cell subsets in Systemic Sclerosis patients show features of exhaustion and reduced anti-fibrotic activities

Abstract Systemic Sclerosis (SSc) or Scleroderma is a chronic autoimmune disease where immune cells contribute to the initiation and/or progression of microvascular damage and fibrosis, leading devastating tissue malfunction often resulting in high morbidity mortality. We recently discovered that PBMCs from SSc patients show increased expression various co-inhibitory receptors, consistent with presence state activation dysfunction. Here, we sought identify functionally characterize dysregulated T cell subsets SSc, determine their role pathogenic fibroblast activation. used multi-parameter spectral flow cytometry vitro cell/fibroblast co-culture assays understand dysfunction exhaustion using clinical samples well-defined cohort patients. Our immunophenotyping analysis revealed populations features exhaustion, such as enhanced receptors PD-1 TIGIT, reduced production anti-fibrotic cytokine IFN-γ. PD-1+TIGIT+ were found peripheral blood well lung skin In addition, significant reduction expressing transcription factor T-bet patients, suggesting counteract pro-fibrotic Type 2 response SSc. support this, isolated showed capacity limit collagen co-cultures. Together, our data suggest activities are driven into enabling fibrosis. Supported by grants NIH (R21 AR071580) National Foundation (Walter & Marie Coyle Research Grant)