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The Late Endosomal Adaptor Molecule p14 (LAMTOR2) Regulates TGFβ1-Mediated Homeostasis of Langerhans Cells.

Authors :
Sparber, Florian
Tripp, Christoph H
Komenda, Kerstin
Scheffler, Julia M
Clausen, Björn E
Huber, Lukas A
Romani, Nikolaus
Stoitzner, Patrizia
Source :
Journal of Investigative Dermatology. Jan2015, Vol. 135 Issue 1, p119-129. 11p.
Publication Year :
2015

Abstract

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 β1 (TGFβ1) pathway, by lowering TGFβ receptor II expression on BMDCs and LCs, as well as surface binding of TGFβ1 on BMDCs. We conclude that p14 deficiency affects TGFβ1 sensitivity of LCs, which is mandatory for their homeostasis and subsequently for their immunological function during CHS. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
0022202X
Volume :
135
Issue :
1
Database :
Academic Search Index
Journal :
Journal of Investigative Dermatology
Publication Type :
Academic Journal
Accession number :
99922423
Full Text :
https://doi.org/10.1038/jid.2014.324