PMID- 32286311
OWN - NLM
STAT- MEDLINE
DCOM- 20200721
LR  - 20211204
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 11
IP  - 1
DP  - 2020 Apr 14
TI  - Kinesin-1 regulates antigen cross-presentation through the scission of 
      tubulations from early endosomes in dendritic cells.
PG  - 1817
LID - 10.1038/s41467-020-15692-0 [doi]
LID - 1817
AB  - Dendritic cells (DCs) constitute a specialized population of immune cells that 
      present exogenous antigen (Ag) on major histocompatibility complex (MHC) class I 
      molecules to initiate CD8 + T cell responses against pathogens and tumours. 
      Although cross-presentation depends critically on the trafficking of 
      Ag-containing intracellular vesicular compartments, the molecular machinery that 
      regulates vesicular transport is incompletely understood. Here, we demonstrate 
      that mice lacking Kif5b (the heavy chain of kinesin-1) in their DCs exhibit a 
      major impairment in cross-presentation and thus a poor in vivo anti-tumour 
      response. We find that kinesin-1 critically regulates antigen cross-presentation 
      in DCs, by controlling Ag degradation, the endosomal pH, and MHC-I recycling. 
      Mechanistically, kinesin-1 appears to regulate early endosome maturation by 
      allowing the scission of endosomal tubulations. Our results highlight kinesin-1's 
      role as a molecular checkpoint that modulates the balance between antigen 
      degradation and cross-presentation.
FAU - Belabed, Meriem
AU  - Belabed M
AD  - Universite de Paris, Imagine Institute, Laboratory of Molecular basis of altered 
      immune homeostasis, INSERM UMR1163, F-75015, Paris, France.
FAU - Mauvais, Francois-Xavier
AU  - Mauvais FX
AUID- ORCID: 0000-0002-5240-4280
AD  - Universite de Paris, INSERM, U1151, Institut Necker Enfants Malades; Universite 
      de Paris; CNRS, UMR8253, F-75015, Paris, France.
FAU - Maschalidi, Sophia
AU  - Maschalidi S
AD  - Universite de Paris, Imagine Institute, Laboratory of Molecular basis of altered 
      immune homeostasis, INSERM UMR1163, F-75015, Paris, France.
FAU - Kurowska, Mathieu
AU  - Kurowska M
AD  - Universite de Paris, Imagine Institute, Laboratory of Molecular basis of altered 
      immune homeostasis, INSERM UMR1163, F-75015, Paris, France.
FAU - Goudin, Nicolas
AU  - Goudin N
AD  - Cell Imaging Facility, Universite de Paris, Imagine Institute, F-75015, Paris, 
      France.
FAU - Huang, Jian-Dong
AU  - Huang JD
AUID- ORCID: 0000-0001-7531-2816
AD  - School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of 
      Hong Kong, Hong Kong, China.
FAU - Fischer, Alain
AU  - Fischer A
AD  - Universite de Paris, Imagine Institute, Laboratory of Molecular basis of altered 
      immune homeostasis, INSERM UMR1163, F-75015, Paris, France.
AD  - Immunology and Pediatric Hematology Department, Necker Children's Hospital, 
      AP-HP, F-75015, Paris, France.
AD  - College de France, F-75005, Paris, France.
FAU - de Saint Basile, Genevieve
AU  - de Saint Basile G
AD  - Universite de Paris, Imagine Institute, Laboratory of Molecular basis of altered 
      immune homeostasis, INSERM UMR1163, F-75015, Paris, France.
FAU - van Endert, Peter
AU  - van Endert P
AUID- ORCID: 0000-0003-3782-0750
AD  - Universite de Paris, INSERM, U1151, Institut Necker Enfants Malades; Universite 
      de Paris; CNRS, UMR8253, F-75015, Paris, France.
FAU - Sepulveda, Fernando E
AU  - Sepulveda FE
AUID- ORCID: 0000-0001-5865-4929
AD  - Universite de Paris, Imagine Institute, Laboratory of Molecular basis of altered 
      immune homeostasis, INSERM UMR1163, F-75015, Paris, France.
AD  - Centre national de la recherche scientifique (CNRS), F-75015, Paris, France.
FAU - Menasche, Gael
AU  - Menasche G
AUID- ORCID: 0000-0001-6671-3642
AD  - Universite de Paris, Imagine Institute, Laboratory of Molecular basis of altered 
      immune homeostasis, INSERM UMR1163, F-75015, Paris, France. 
      gael.menasche@inserm.fr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200414
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Acids)
RN  - 0 (Antigens)
RN  - 0 (Antigens, CD)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 9006-59-1 (Ovalbumin)
RN  - EC 3.6.4.4 (Kinesins)
SB  - IM
MH  - Acids/metabolism
MH  - Animals
MH  - Antigen Presentation/*immunology
MH  - Antigens/metabolism
MH  - Antigens, CD/metabolism
MH  - Bone Marrow Cells/cytology
MH  - Cell Proliferation
MH  - Dendritic Cells/*metabolism
MH  - Endocytosis
MH  - Endosomes/*metabolism
MH  - Histocompatibility Antigens Class I/metabolism
MH  - Kinesins/deficiency/*metabolism
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Microtubules/metabolism
MH  - Neoplasms/pathology
MH  - Ovalbumin/immunology
MH  - Solubility
PMC - PMC7156633
COIS- The authors declare no competing interests.
EDAT- 2020/04/15 06:00
MHDA- 2020/07/22 06:00
PMCR- 2020/04/14
CRDT- 2020/04/15 06:00
PHST- 2019/05/31 00:00 [received]
PHST- 2020/03/25 00:00 [accepted]
PHST- 2020/04/15 06:00 [entrez]
PHST- 2020/04/15 06:00 [pubmed]
PHST- 2020/07/22 06:00 [medline]
PHST- 2020/04/14 00:00 [pmc-release]
AID - 10.1038/s41467-020-15692-0 [pii]
AID - 15692 [pii]
AID - 10.1038/s41467-020-15692-0 [doi]
PST - epublish
SO  - Nat Commun. 2020 Apr 14;11(1):1817. doi: 10.1038/s41467-020-15692-0.