期刊
JOURNAL OF INVESTIGATIVE DERMATOLOGY
卷 135, 期 1, 页码 119-129出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/jid.2014.324
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资金
- Austrian Science Fund [FWF-P23548, FWF-P21487, SFB021]
- IFTZ project of the Innsbruck Medical University [11]
- Austrian Science Fund (FWF) [P21487, P23548] Funding Source: Austrian Science Fund (FWF)
- Austrian Science Fund (FWF) [P 23548, P 21487] Funding Source: researchfish
Langerhans cells (LCs), a sub-population of dendritic cells (DCs) in the skin, participate in the regulation of immunity and peripheral tolerance. The adaptor molecule p14 is part of the late endosomal/lysosomal adaptor and mitogen-activated protein kinase and mammalian target of rapamycin (mTOR) activator/regulator (LAMTOR) complex, which mediates the activation of lysosome-associated extracellular signaling regulated kinase (ERK) and the mTOR cascade. In previous work, we demonstrated that CD11c-specific deficiency of p14 disrupts LC homeostasis by affecting the LAMTOR-mediated ERK and mTOR signaling. In this study, we extended our analysis on p14 deficiency specifically in LCs. Langerin-specific ablation of p14 caused a complete loss of LCs, accompanied by an increased maturational phenotype of LCs. The absence of LCs in p14-deficient mice reduced contact hypersensitivity (CHS) responses to the contact sensitizer trinitrochlorobenzene. Analysis using bone marrow derived DCs (BMDCs) revealed that p14 deficiency in DCs/LCs interfered with the LC-relevant transforming growth factor beta 1 (TGF beta 1) pathway, by lowering TGF beta receptor II expression on BMDCs and LCs, as well as surface binding of TGF beta 1 on BMDCs. We conclude that p14 deficiency affects TGF beta 1 sensitivity of LCs, which is mandatory for their homeostasis and subsequently for their immunological function during CHS.
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