PMID- 31659013
OWN - NLM
STAT- MEDLINE
DCOM- 20200527
LR  - 20211204
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 203
IP  - 11
DP  - 2019 Dec 1
TI  - Downregulation of MHC Class II by Ubiquitination Is Required for the Migration of 
      CD206(+) Dendritic Cells to Skin-Draining Lymph Nodes.
PG  - 2887-2898
LID - 10.4049/jimmunol.1900593 [doi]
AB  - Dendritic cells (DCs) are critical players in skin homeostasis. A subset of 
      mannose receptor (CD206)-expressing monocyte-derived DCs was found in skin, and 
      their migratory counterpart is present in skin-draining lymph nodes (sdLNs). Skin 
      CD206(+) DCs were shown to upregulate MHC class II (MHCII) progressively, raising 
      the question of whether this feature affects their biology. In this study, we 
      assessed the role of MHCII regulation in the development and migration of these 
      cells in mouse models expressing differential MHCII levels. Using CD206 as a 
      surrogate marker, we found that skin CD206(+) DCs develop in an MHCII-independent 
      manner. However, their migration to sdLNs was affected by overexpression rather 
      than absence or lower expression of MHCII. Accordingly, B16 tumor growth was 
      exacerbated in mice overexpressing MHCII in the absence of ubiquitination. 
      Mechanistically, CD206(+) DCs from these mice showed decreased IRF4 and CCR7 
      expression. LPS, which is known to promote monocyte-derived DC recruitment to 
      sdLNs, partially improved these defects. However, GM-CSF delivery restored 
      CD206(+) DC migration by promoting IRF4 expression. Collectively, these data show 
      that MHCII downregulation is crucial for IRF4-dependent migration of CD206(+) DCs 
      to sdLNs in health and disease.
CI  - Copyright (c) 2019 by The American Association of Immunologists, Inc.
FAU - Majdoubi, Abdelilah
AU  - Majdoubi A
AUID- ORCID: 0000-0002-2053-4793
AD  - Departement de Microbiologie, Infectiologie et Immunologie, Universite de 
      Montreal, Montreal H3T 1J4, Quebec, Canada.
FAU - Lee, Jun Seong
AU  - Lee JS
AD  - Departement de Microbiologie, Infectiologie et Immunologie, Universite de 
      Montreal, Montreal H3T 1J4, Quebec, Canada.
FAU - Balood, Mohammad
AU  - Balood M
AD  - Departement de Pharmacologie, Universite de Montreal, Montreal H3T 1J4, Quebec, 
      Canada.
FAU - Sabourin, Antoine
AU  - Sabourin A
AD  - Departement de Microbiologie, Infectiologie et Immunologie, Universite de 
      Montreal, Montreal H3T 1J4, Quebec, Canada.
FAU - DeMontigny, Auriane
AU  - DeMontigny A
AUID- ORCID: 0000-0003-0429-6374
AD  - Departement de Microbiologie, Infectiologie et Immunologie, Universite de 
      Montreal, Montreal H3T 1J4, Quebec, Canada.
FAU - Kishta, Osama A
AU  - Kishta OA
AUID- ORCID: 0000-0003-2420-2726
AD  - Departement de Microbiologie, Infectiologie et Immunologie, Universite de 
      Montreal, Montreal H3T 1J4, Quebec, Canada.
FAU - Moulefera, Mohamed Abdelwafi
AU  - Moulefera MA
AUID- ORCID: 0000-0002-9335-5761
AD  - Departement de Microbiologie, Infectiologie et Immunologie, Universite de 
      Montreal, Montreal H3T 1J4, Quebec, Canada.
FAU - Galbas, Tristan
AU  - Galbas T
AD  - Departement de Microbiologie, Infectiologie et Immunologie, Universite de 
      Montreal, Montreal H3T 1J4, Quebec, Canada.
FAU - Yun, Tae Jin
AU  - Yun TJ
AD  - Institut de Recherches Cliniques de Montreal, Montreal H2W 1R7, Quebec, Canada; 
      and.
FAU - Talbot, Sebastien
AU  - Talbot S
AUID- ORCID: 0000-0001-9932-7174
AD  - Departement de Pharmacologie, Universite de Montreal, Montreal H3T 1J4, Quebec, 
      Canada.
FAU - Ishido, Satoshi
AU  - Ishido S
AD  - Department of Microbiology, Hyogo College of Medicine, Nishinomiya, Hyogo 
      663-8501, Japan.
FAU - Cheong, Cheolho
AU  - Cheong C
AD  - Institut de Recherches Cliniques de Montreal, Montreal H2W 1R7, Quebec, Canada; 
      and.
FAU - Thibodeau, Jacques
AU  - Thibodeau J
AUID- ORCID: 0000-0002-0790-9634
AD  - Departement de Microbiologie, Infectiologie et Immunologie, Universite de 
      Montreal, Montreal H3T 1J4, Quebec, Canada; Jacques.thibodeau@umontreal.ca.
LA  - eng
GR  - MOP 136802/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191028
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Mannose Receptor)
RN  - 0 (Mannose-Binding Lectins)
RN  - 0 (Receptors, Cell Surface)
SB  - IM
MH  - Animals
MH  - *Cell Movement
MH  - Dendritic Cells/*metabolism
MH  - *Down-Regulation
MH  - Histocompatibility Antigens Class II/*metabolism
MH  - Lectins, C-Type/*metabolism
MH  - Lymph Nodes/*metabolism
MH  - Mannose Receptor
MH  - Mannose-Binding Lectins/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Receptors, Cell Surface/*metabolism
MH  - Skin/*metabolism
MH  - *Ubiquitination
EDAT- 2019/10/30 06:00
MHDA- 2020/05/28 06:00
CRDT- 2019/10/30 06:00
PHST- 2019/05/23 00:00 [received]
PHST- 2019/09/20 00:00 [accepted]
PHST- 2019/10/30 06:00 [pubmed]
PHST- 2020/05/28 06:00 [medline]
PHST- 2019/10/30 06:00 [entrez]
AID - jimmunol.1900593 [pii]
AID - 10.4049/jimmunol.1900593 [doi]
PST - ppublish
SO  - J Immunol. 2019 Dec 1;203(11):2887-2898. doi: 10.4049/jimmunol.1900593. Epub 2019 
      Oct 28.