Mechanistic target of rapamycin complex 1 is involved in psoriasis and regulated by anti‐TNF‐α treatment

Abstract

The mechanistic target of rapamycin (mTOR) acts through two distinct signalling complexes,\ud known as mTOR complex (mTORC) 1 and mTORC2. One of the main upstream regulator of\ud mTORC1 is tumour necrosis factor (TNF)-α, an important pro-inflammatory cytokine involved in\ud psoriasis. When active, mTORC1 phosphorylates and activates its downstream effector ribosomal protein S6 kinase 1 (S6K1) which is also found increased in psoriasis. Thus, the aim of the study\ud was to assess the involvement of mTORC1 signalling as well as to shed a light on the possible\ud relationship between mTORC1 and TNF-α in psoriasis. Our results showed that mTOR, S6K1 and,\ud in particular, its active form P-S6K1 were increased in psoriatic plaque, suggesting a specific\ud involvement of mTORC1 pathway in the disease. Moreover, for the first time, we reported that PS6K1\ud was completely abolished after anti-TNF-α therapy, indicating a stronger action of anti-TNF-\ud α agent on mTORC1

Anti‐TNF‐α therapy modulates mTORC1 signalling in hidradenitis suppurativa

“…This difference was stronger regarding the activated form, P-S6K1, highlighting the specific involvement of mTORC1 in HS pathogenesis. Our observed mTOR increase in HS lesional skin is in line with our previous evidences 4,5,8,9 and is supported by the fact that TNF-a modulates several targets including mTOR pathway. Indeed, TNF-a suppresses tuberous sclerosis (TSC) 1 resulting in mTORC1 activation.…”

T helper 17 cell/regulatory T-cell imbalance in hidradenitis suppurativa/acne inversa: the link to hair follicle dissection, obesity, smoking and autoimmune comorbidities

“…TNF‐α activates kinase of inhibitor of kappa light chain gene enhancer in B cells, which inactivates hamartin (also known as tuberous sclerosis 1), a key negative regulator of mTORC1 . In psoriasis vulgaris, adalimumab treatment decreased mTORC1 activity, which is required for mTORC1‐mediated proinflammatory cytokine production (Fig. b) …”

Sirolimus treatment for cirrhosis or hepatocellular carcinoma patients accompanied by psoriasis after liver transplantation: A single center experience

“…So, when these patients were treated in our center, they all had a lengthy PS history and had been treated in hospital, our diagnosis was based on the earlier diagnosis and treatment of patients by a specialist. Meanwhile, combined with the patient's history including the PASI score, we confirmed the diagnosis and excluded other nonspecific infections with the laboratory (hematological examination, cultivation of the dander ( 11 , 23 , 24 , 26 , 27 ) and imaging (CT and MRI scanning) diagnosis methodology.…”