Activation of the aryl hydrocarbon receptor alleviates Sjögren's syndrome by promoting Bregs differentiation

The aryl hydrocarbon receptor (AhR) is involved in the regulation of inflammation and maintenance of immune homeostasis. However, the role of AhR in the pathogenesis of autoimmune diseases, especially in Sjögren's syndrome (SS) remains unclear. Sjögren's syndrome mice model induced by using salivary gland proteins and Complete Freund's Adjuvant, we found that after activation of AhR with 6-formylindolo [3,2-b] carbazole (FICZ), salivary gland lymphocyte infiltration and saliva flow rates were significantly alleviated. And the percents and numbers of GCB cells, plasma cells (PC), and plasmablast cells (PBC) were significantly decreased but the percents of regulatory B cells (Bregs) were significantly increased in model mice treated with FICZ. Moreover, the proportions of Th1 and Th17 cells were also reduced after being treated with FICZ. Indeed, these changes were recovered in B-cell-specific AhR knock-out mice. Overall, our study provides a new strategy that AhR activation alleviates Sjögren's syndrome by promoting Bregs differentiation thereby inhibiting both humoral and cellular immunity responses, which provides new insights for the future therapy of Sjögren's syndrome.