PMID- 25078666
OWN - NLM
STAT- MEDLINE
DCOM- 20150226
LR  - 20231107
IS  - 1523-1747 (Electronic)
IS  - 0022-202X (Print)
IS  - 0022-202X (Linking)
VI  - 135
IP  - 1
DP  - 2015 Jan
TI  - The late endosomal adaptor molecule p14 (LAMTOR2) regulates TGFbeta1-mediated 
      homeostasis of Langerhans cells.
PG  - 119-129
LID - S0022-202X(15)37043-3 [pii]
LID - 10.1038/jid.2014.324 [doi]
AB  - 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 beta1 (TGFbeta1) pathway, by lowering TGFbeta receptor II expression on 
      BMDCs and LCs, as well as surface binding of TGFbeta1 on BMDCs. We conclude that p14 
      deficiency affects TGFbeta1 sensitivity of LCs, which is mandatory for their 
      homeostasis and subsequently for their immunological function during CHS.
FAU - Sparber, Florian
AU  - Sparber F
AD  - Department of Dermatology and Venereology, Innsbruck Medical University, 
      Innsbruck, Austria.
FAU - Tripp, Christoph H
AU  - Tripp CH
AD  - Department of Dermatology and Venereology, Innsbruck Medical University, 
      Innsbruck, Austria.
FAU - Komenda, Kerstin
AU  - Komenda K
AD  - Department of Dermatology and Venereology, Innsbruck Medical University, 
      Innsbruck, Austria.
FAU - Scheffler, Julia M
AU  - Scheffler JM
AD  - Division of Cell Biology, Biocenter Innsbruck, Innsbruck, Austria.
FAU - Clausen, Bjorn E
AU  - Clausen BE
AD  - Institute for Molecular Medicine, University Medical Center of the Johannes 
      Gutenberg-University Mainz, Mainz, Germany.
FAU - Huber, Lukas A
AU  - Huber LA
AD  - Division of Cell Biology, Biocenter Innsbruck, Innsbruck, Austria.
FAU - Romani, Nikolaus
AU  - Romani N
AD  - Department of Dermatology and Venereology, Innsbruck Medical University, 
      Innsbruck, Austria.
FAU - Stoitzner, Patrizia
AU  - Stoitzner P
AD  - Department of Dermatology and Venereology, Innsbruck Medical University, 
      Innsbruck, Austria. Electronic address: patrizia.stoitzner@i-med.ac.at.
LA  - eng
GR  - P 21487/FWF_/Austrian Science Fund FWF/Austria
GR  - P 23548/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140731
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (CD11c Antigen)
RN  - 0 (LAMTOR2 protein, mouse)
RN  - 0 (Proteins)
RN  - 0 (Receptors, Transforming Growth Factor beta)
RN  - 0 (Tgfb1 protein, mouse)
RN  - 0 (Transforming Growth Factor beta1)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type I)
RN  - EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type II)
SB  - IM
MH  - Animals
MH  - CD11c Antigen/genetics/immunology/metabolism
MH  - Cell Movement/immunology
MH  - Dermatitis, Contact/genetics/*immunology/metabolism
MH  - Down-Regulation/immunology
MH  - Endosomes/immunology/metabolism
MH  - Female
MH  - Homeostasis/immunology
MH  - Immune Tolerance/immunology
MH  - Immunophenotyping
MH  - Langerhans Cells/*immunology/metabolism
MH  - MAP Kinase Signaling System/*immunology
MH  - Male
MH  - Mice, Mutant Strains
MH  - Protein Serine-Threonine Kinases/genetics/immunology/metabolism
MH  - Proteins/genetics/*immunology/metabolism
MH  - Receptor, Transforming Growth Factor-beta Type I
MH  - Receptor, Transforming Growth Factor-beta Type II
MH  - Receptors, Transforming Growth Factor beta/genetics/immunology/metabolism
MH  - Skin/*immunology/metabolism
MH  - Transforming Growth Factor beta1/*immunology/metabolism
PMC - PMC4285575
MID - EMS61605
OID - NLM: EMS61605
EDAT- 2014/08/01 06:00
MHDA- 2015/02/27 06:00
PMCR- 2015/07/01
CRDT- 2014/08/01 06:00
PHST- 2014/01/27 00:00 [received]
PHST- 2014/06/18 00:00 [revised]
PHST- 2014/06/30 00:00 [accepted]
PHST- 2014/08/01 06:00 [entrez]
PHST- 2014/08/01 06:00 [pubmed]
PHST- 2015/02/27 06:00 [medline]
PHST- 2015/07/01 00:00 [pmc-release]
AID - S0022-202X(15)37043-3 [pii]
AID - 10.1038/jid.2014.324 [doi]
PST - ppublish
SO  - J Invest Dermatol. 2015 Jan;135(1):119-129. doi: 10.1038/jid.2014.324. Epub 2014 
      Jul 31.