Antigen-independent, fibroblast-mediated Ttek activation drives acinar dysfunction in Sjögren’s Disease before lymphocytic infiltration

Acinar cells are responsible for saliva manufacture. When we probed the acinar transcriptome in the parotid SG of SjD patients without lymphocytic infiltration (patients with a focus score of 0, “FS0”), we observed acinar gene dysregulation, interferon signature presence and fewer but larger mitochondria than controls.

Cell-cell communication analysis suggested that fibroblasts expressing CXCL12 and/or extracellular matrix (ECM) proteins (collagens, laminin, fibronectin) communicate with tissue resident CD8+ T cells (Trm) and/or CD8+ granzyme K+ T cells (“Tteks”), in FS0 SjD SGs. Podoplanin+ and vimentin+ fibroblasts were localized close to CD8+granzyme K+ Tteks in FS0 SjD SGs, amongst acinar cells. CD8+CD27- T cells exposed to CXCL12 and the ECM component collagen increased granzyme K+ expression, without concurrent T cell receptor stimulation.