Increased Mtorc1 Activation In Salivary Gland B Cells And T Cells From Patients With Sjogren'S Syndrome: Mtor Inhibition As A Novel Therapeutic Strategy To Halt Immunopathology?

### Key messages#### What is already known about this subject?#### What does this study add?#### How might this impact on clinical practice?Primary Sjogren’s syndrome (pSS) is a systemic autoimmune disorder characterised by lymphocytic infiltration and dysfunction of exocrine glands. lymphocytic infiltrates in exocrine glands mainly consist of Th cells and B cells. A hallmark feature of pSS is B cell hyperactivity, including formation of autoantibodies, elevated serum IgG levels, increased numbers of B cells and IgG+/IgM+ plasma cells in salivary glands, and formation of germinal centre-like structures in the salivary glands associated with an increased risk of lymphoma development.1 2 Th cells and in particular T follicular helper (Tfh) cells play an important role in activation of B cells and formation of germinal centre-like structures.1 The mammalian/mechanistic target of rapamycin (mTOR) pathway is essential for growth, survival and proliferation of T and B cells and integrates multiple signals from the immune microenvironment, including growth factors, nutrients,and T cell receptor (TCR)/B cell receptor (BCR) engagement.3 4 serine/threonine kinase mTOR is the catalytic subunit of two distinct complexes: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), characterised by the incorporation of the proteins Raptor and Rictor, respectively. mTORC1 is generally described to play a role in protein translation, cell growth, proliferation and metabolism, whereas mTORC2 regulates metabolism, cell survival, rearrangement of the cytoskeleton and cell cycle progression (figure 1A).4 Figure 1 Decreased mammalian/mechanistic target of rapamycin (mTOR) pathway-related gene and protein expression in circulating B cells from patients with pSS . …