sirolimus and Polymyositis

Peripheral blood T lymphocytopenia has previously been identified in polymyositis/dermatomyositis (PM/DM) patients. Therefore, the present study aimed to examine the potential role of autophagy in peripheral blood T cell survival in PM/DM patients. Transmission electron microscopy was used to detect the formation of autophagosomes of peripheral blood cluster of differentiation (CD)3+ T cells obtained from 24 patients with PM/DM and 21 healthy controls. Protein and mRNA expression levels of autophagy‑related molecules were examined by western blot analysis and reverse transcription‑quantitative polymerase chain reaction, respectively. The number of peripheral blood CD3+ T cells decreased significantly in PM/DM patients. The median percentage of apoptosis of CD3+ T cells in PM/DM patients was significantly increased compared with healthy controls. Furthermore, the number of autophagosomes and the expression of the autophagy markers microtubule‑associated protein 1A/1B‑light chain 3 (LC3) and Beclin‑1 were significantly reduced in the circulating CD3+ T cells of PM/DM patients compared with those of healthy controls. LC3 and Beclin‑1 protein levels correlated negatively with apoptosis rates in circulating CD3+ T cells in patients with PM/DM. CD3+ T cells from PM/DM patients treated with rapamycin increased autophagy and decreased apoptosis compared with untreated cells (P<0.05). In conclusion, these results suggested that autophagy may serve a potential protective role in the peripheral blood T cells of patients with PM/DM.

Topics: Adult; Aged; Apoptosis; Autophagy; Case-Control Studies; CD3 Complex; Cell Separation; Cell Survival; Dermatomyositis; Female; Humans; Lymphocyte Subsets; Male; Middle Aged; Polymyositis; Sirolimus; T-Lymphocytes; Young Adult

Polymyositis (PM) is a chronic disease characterized by muscle pain, weakness, and increase in muscle-related enzymes, accompanied with inflammations in lymphocytes. However, it is not well understood how the molecular alternations in lymphocytes contribute to the development of polymyositis. The mechanistic target of rapamycin (mTOR) signaling is the central regulator of metabolism and inflammation in mammalian cells. Based on previous studies, we proposed that mTOR signaling may control inflammatory reactions

Topics: Biomarkers; Cells, Cultured; Fatty Acids, Monounsaturated; Humans; Leukocytes, Mononuclear; Lipid Metabolism; Molecular Targeted Therapy; Polymyositis; Signal Transduction; Sirolimus; TOR Serine-Threonine Kinases