Single-cell analysis reveals sexually dimorphic repertoires of Interferon-γ and IL-17A producing T cells in salivary glands of Sjögren's syndrome mice.

The development of Sjögren's syndrome (SjS) is a dynamic and temporal process with a female predilection. Following the initial influx of immune cells, T cell clusters develop, accelerating the pathology in the salivary glands. Proinflammatory cytokines, IFN-γ and IL-17A, produced by T cells contribute synergistically to the disease. In this study, we examined the sexual dimorphism in cellular infiltrates of the salivary glands by using functional single-cell microengraving analysis. Using high-throughput sequencing, we investigated the clonal diversity of the T cell receptors (TCRs) of infiltrating IFN-γ and IL-17A-producing T cells in male and female SjS-susceptible (SjS) C57BL/6.NOD-Aec1Aec2 mice. There were elevated frequencies of IFN-γ and IL-17A-producing effector T cell populations in female SjS mice compared to male SjS mice. MEME analysis shows high frequency and unique, sexually dimorphic motifs in the TCR hypervariable regions in the SjS mice. Male mice selected for TRAV8/TRAJ52 (CATDLNTGANTGKLTFG) TCR genes in Th1 cells and TRBV16/(TRBD1/2)TRBJ1-7 (CGGKRRLESIFR) in Th1 and Th17 cells. Female SjS mice selected for TRAV8/TRAJ52 (CATDLNTGANTGKLTFG), TRAV13D-2/TRAJ23 (CVYLEHHFE), and TRBV23/(TRBD2)TRBJ2-2 (CRKLHSCATCALNFL) in Th1 cells. These findings suggest that there is an elevated prevalence of pathogenic effector T cells in the glands with a sexually dimorphic selection bias of TCR repertoires.