Antiviral State of CD1c+ cDC contributes to Increased Maturation and Activation of Cytotoxic Natural Killer cells in Sjögren’s Syndrome

Abstract

Objective: Primary Sjogrens syndrome (pSS) is an inflammatory autoimmune disorder characterized by damage of exocrine glands and linked to IFN responses and the induction of autoreactive adaptive immune cells. However, the role of innate immune cells in pSS pathology remains understudied. Methods: We studied differential phenotypical characteristics of different NK cell, conventional dendritic cell (cDC) and monocyte subsets in the blood and salivary glands from pSS individuals. Transcriptional patterns of circulating cDC and Mo from pSS and healthy controls were also compared. Finally, in vivo alterations in these cell populations in the salivary gland were investigated in a mouse model. Results: Here, we identified CD16+ CD56hi NK cells enriched in pSS patients which associates with higher natural cytotoxic function and increased proportions of circulating CD64+ CD1c+ cDC exhibiting antiviral transcriptional IFN signatures. CD64hi cDC and NK cell were detected infiltrated into the salivary glands from pSS patients and a murine SS model. CD1c+ cDC from patients with pSS expressed high levels of ligands for activating NK receptors and increased ability to activate NK cells ex vivo. Finally, the antiviral RIG-I and DDX60 sensors regulated the expression of NK cell receptor ligands on CD1c+ cDC. Conclusions: Therefore, the interplay of CD1c+ cDCs and NK cells could contribute to pSS pathology.