Activation of mTOR has been implicated in a number of chronic inflammatory diseases, especially rheumatic diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), sjögren syndrome (SS) and seronegative spondyloarthropathy (SpA).
In addition, the mammalian target of rapamycin complex 1 (mTORC1) pathway was remarkably activated in lupus AtMs, and blocking mTORC1 signalling by rapamycin abolished the generation of T-bet<sup>+</sup> B cells and terminal differentiation of lupus AtMs.
Inhibition of the mammalian target of rapamycin (mTOR) pathway by sirolimus, a drug approved and in clinical use to prevent transplant rejection, has shown promising effects in lupus animal models as well as in patients with both antiphospholipid syndrome and SLE.
Here, western blot analysis was used to detect the level of NLRP3 components and mTORC1/2 substrate in the kidney tissues from B6.MRL-FASlpr/J lupus mice and C57BL/6 mice, and the results showed that mammalian target of rapamycin (mTOR) complex 1/2 (mTORC1/2) and the NLRP3 inflammasome were hyperactivated in B6.MRL-FASlpr/J lupus mice.
Follow-up placebo-controlled clinical trials in diverse patient populations are warranted to further define the role of mTOR blockade in treatment of systemic lupus erythematosus.
Activities of mTOR complexes 1 (mTORC1) and 2 (mTORC2) were examined by quantifying phosphorylation of translation initiation factor 4E-binding protein 1, S6 kinase, and Akt in SLE patients relative to age- and sex-matched female healthy control subjects.
Therefore, we review here the pathways that control ROS production and mTOR activation and identify targets for safe therapeutic modulation of the signaling network that underlies autoimmune diseases, focusing on SLE.
Taken together, metformin-induced alterations in AMPK-mTOR-STAT3 signaling may have therapeutic value in SLE by inhibiting B cell differentiation into PCs and GCs.
Therapeutic approaches aimed at glutathione depletion and mTOR pathway activation appear to be safe and effective for treating lupus, while an opposing intervention may be of benefit in rheumatoid arthritis.
Our exploratory analysis provides evidence that phosphoinositol 3 kinase and mammalian target of rapamycin (mTOR) inhibitors could be potential therapeutic options in SLE worth further future testing.
In turn, mTOR can modify epigenetic pathways including methylation, demethylation, and histone phosphorylation and mediates enhanced T-cell activation in SLE.
The mammalian target of rapamycin, which is a sensor of the mitochondrial transmembrane potential, has been successfully targeted for treatment of SLE with rapamycin or sirolimus in both patients and animal models.
MHP, increased activity of mTOR, Rab GTPases, and Syk kinases, and enhanced Ca2+ flux have emerged as common T and B cell biomarkers and targets for treatment in SLE.
The mammalian target of rapamycin in T and B cells has been successfully targeted for treatment of SLE with rapamycin or sirolimus both in patients and animal models.
In this article, we show that activity of the mammalian target of rapamycin (mTOR), which is a sensor of the mitochondrial transmembrane potential, is increased in lupus T cells.