mTORC1 Deficiency Prevents the Development of MC903-Induced Atopic Dermatitis through the Downregulation of Type 2 Inflammation

被引:3
作者
Gupta, Anupriya [1 ]
Lee, Keunwook [2 ]
Oh, Kwonik [1 ,3 ]
机构
[1] Hallym Univ, Coll Med, Dept Pathol, Chunchon 24252, South Korea
[2] Hallym Univ, Dept Biomed Sci, Chunchon 24252, South Korea
[3] Hallym Univ, Inst Med Sci, Coll Med, Chunchon 24252, South Korea
基金
新加坡国家研究基金会;
关键词
atopic dermatitis; dimethyloxalylglycine (DMOG); hypoxia inducible factor (HIF); MC903; mTORC; TSLP; THYMIC STROMAL LYMPHOPOIETIN; DIFFERENTIATION; CELLS; VITAMIN-D3; RAPAMYCIN; EXPRESSION; CYTOKINES; TSLP; PROLIFERATION; KERATINOCYTES;
D O I
10.3390/ijms24065968
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by eczema and itching. Recently, mTORC, a central regulator of cellular metabolism, has been reported to play a critical role in immune responses, and manipulation of mTORC pathways has emerged as an effective immunomodulatory drug. In this study, we assessed whether mTORC signaling could contribute to the development of AD in mice. AD-like skin inflammation was induced by a 7-day treatment of MC903 (calcipotriol), and ribosomal protein S6 was highly phosphorylated in inflamed tissues. MC903-induced skin inflammation was ameliorated significantly in Raptor-deficient mice and exacerbated in Pten-deficient mice. Eosinophil recruitment and IL-4 production were also decreased in Raptor deficient mice. In contrast to the pro-inflammatory roles of mTORC1 in immune cells, we observed an anti-inflammatory effect on keratinocytes. TSLP was upregulated in Raptor deficient mice or by rapamycin treatment, which was mediated by hypoxia-inducible factor (HIF) signaling. Taken together, these results from our study indicate the dual roles of mTORC1 in the development of AD, and further studies on the role of HIF in AD are warranted.
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页数:12
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