Open AccessSingle-cell analysis reveals sexually dimorphic repertoires of Interferon-γ and IL-17A producing T cells in salivary glands of Sjögren’s syndrome mice
Author(s) -
Arun Wanchoo,
Alexandria Voigt,
Sukesh Sukumaran,
Carol M. Stewart,
Indraneel Bhattacharya,
Cuong Q. Nguyen
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-12627-6
Subject(s) - biology , t cell receptor , t cell , immunology , immune system , proinflammatory cytokine , interleukin 17 , effector , interferon , inflammation
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 s ) C57BL/6.NOD- Aec1Aec2 mice. There were elevated frequencies of IFN-γ and IL-17A-producing effector T cell populations in female SjS S mice compared to male SjS S mice. MEME analysis shows high frequency and unique, sexually dimorphic motifs in the TCR hypervariable regions in the SjS S 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 S 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.