GSE194263
Antiviral State of CD1c+ cDC associates with increased  Natural Killer maturation and activation in Sjögren´s Syndrome
Primary Sjögren´s syndrome (pSS) is a heterogeneous inflammatory autoimmune disorder characterized by the infiltration of different immune subsets in exocrine glands and potential development of extra-glandular manifestations. pSS pathology and glandular tissue destruction have been linked to increased IFN responses and the induction of autoreactive T and B cells. However, association of innate immune cells such as Natural Killer (NK) cells and conventional dendritic cells (cDC) with the tissular damage and IFN environment in pSS remains understudied. Here, we identified higher expression of NKG2D, CD107a and superior cytotoxic function on circulating NK cells from pSS which was associated with significant enrichment in a subpopulation of CD16+CD56Hi NK cells in the blood of these patients. In addition, Granzyme B+ NK cells and MICab+ CD1c+ cDC could be found in proximity in tissue sections of salivary glands from pSS patients. Importantly, murine populations of CD64Hi CD11b+CD11c+ cDC and transitional NKG2Dhi CD11b+CD27+ NK1.1 cells, infiltrated in vivo into the salivary gland in a stablished pSS mouse model. Interestingly, transcriptional IFN signatures present on CD1c+ cDC from pSS are characterized by the upregulation of RIG-I and DDX60 sensors and the ISGs IFIT1 and IFIT3. These transcriptional patterns on CD1c+ cDC associated with high basal expression of MICa/b and SLAMF7 ligands for NK receptors, the Fc receptor CD64 and increased ability to induce maturation and CD107a expression in NK cells. Finally, expression of SLAMF7 and MICa/b after Poly I:C exposure was regulated by RIG-I and DDX60 on CD1c+ cDC.  Therefore, crosstalk between CD1c+ cDCs and NK cells could contribute to the pathogenesis of pSS, and represent new cellular therapeutic targets for treatment of pSS. Overall design: We performed RNA sequencing using RNA from Monocytes, Dendritic Cd1c+ and Dendritic Cd141 cells obtained from blood of Sjögren´s Syndrome versus healthy matched controls. Healthy samples are available in GSE157047 (matched controls are listed in the GSM descriptions).