PMID- 34431547
OWN - NLM
STAT- MEDLINE
DCOM- 20220510
LR  - 20220531
IS  - 1938-3673 (Electronic)
IS  - 0741-5400 (Linking)
VI  - 111
IP  - 4
DP  - 2022 Apr
TI  - The WASp L272P gain-of-function mutation alters dendritic cell coordination of 
      actin dynamics for migration and adhesion.
PG  - 793-803
LID - 10.1002/JLB.1AB0821-013RR [doi]
AB  - Dendritic cells (DCs) devoid of the actin regulator Wiskott-Aldrich syndrome 
      protein (WASp) show reduced directed migration and decreased formation of 
      podosome adhesion structures. We examined DCs expressing a gain-of-function 
      mutation in WASp, WASp L272P, identified in X-linked neutropenia patients. 
      Analysis of WASp L272P DCs was compared to WASp-deficient DCs to examine how WASp 
      activity influences DC migratory responses. In confined space, WASp-deficient DCs 
      had increased migration speed whereas WASp L272P DCs had similar average speed 
      but increased speed fluctuations, reduced displacement, and atypical rounded 
      morphology, compared to wild-type (WT) DCs. Using an ear inflammation model and 
      flow cytometry analysis, WT, WASp-deficient, and WASp L272P DCs were found to 
      migrate in comparable numbers to the draining lymph nodes (LNs). However, 
      histology analysis revealed that migratory DCs of WASp deficient and WASp L272P 
      mice were mainly located in the collagenous capsule of the LN whereas WT DCs were 
      located inside the LN. Analysis of ultrastructural features revealed that WASp 
      L272P DCs had reduced cell area but formed larger podosome structures when 
      compared to WT DCs. Together, our data suggest that WASp activity regulates DC 
      migration and that loss-of-function and gain-of-function in WASp activity lead to 
      different and phenotype-specific DC migratory behavior.
CI  - (c) 2021 The Authors. Journal of Leukocyte Biology published by Wiley Periodicals 
      LLC on behalf of Society for Leukocyte Biology.
FAU - Oliveira, Mariana M S
AU  - Oliveira MMS
AD  - Department of Microbiology Tumor and Cell Biology, Karolinska Institute, 
      Stockholm, Sweden.
FAU - Kung, Shin-Yu
AU  - Kung SY
AD  - Department of Microbiology Tumor and Cell Biology, Karolinska Institute, 
      Stockholm, Sweden.
FAU - Moreau, Helene D
AU  - Moreau HD
AD  - INSERM U932, Institute Curie, Cedex, Paris, France.
FAU - Maurin, Mathieu
AU  - Maurin M
AD  - Institute Curie, PSL Research University, INSERM U932, Paris, France.
FAU - Record, Julien
AU  - Record J
AD  - Department of Microbiology Tumor and Cell Biology, Karolinska Institute, 
      Stockholm, Sweden.
FAU - Sanseau, Doriane
AU  - Sanseau D
AD  - INSERM U932, Institute Curie, Cedex, Paris, France.
FAU - Nylen, Susanne
AU  - Nylen S
AD  - Department of Microbiology Tumor and Cell Biology, Karolinska Institute, 
      Stockholm, Sweden.
FAU - Lennon-Dumenil, Ana-Maria
AU  - Lennon-Dumenil AM
AD  - INSERM U932, Institute Curie, Cedex, Paris, France.
FAU - Westerberg, Lisa S
AU  - Westerberg LS
AD  - Department of Microbiology Tumor and Cell Biology, Karolinska Institute, 
      Stockholm, Sweden.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210825
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Actins)
RN  - 0 (Was protein, mouse)
RN  - 0 (Wiskott-Aldrich Syndrome Protein)
SB  - IM
MH  - Actins/metabolism
MH  - Animals
MH  - Cell Movement/physiology
MH  - Dendritic Cells/metabolism
MH  - Gain of Function Mutation
MH  - Humans
MH  - Mice
MH  - *Neutropenia/genetics
MH  - Wiskott-Aldrich Syndrome Protein/*genetics/metabolism
OTO - NOTNLM
OT  - WASp
OT  - X-linked neutropenia
OT  - actin
OT  - dendritic cells
OT  - microchannels
OT  - migration
EDAT- 2021/08/26 06:00
MHDA- 2022/05/11 06:00
CRDT- 2021/08/25 08:50
PHST- 2021/08/26 06:00 [pubmed]
PHST- 2022/05/11 06:00 [medline]
PHST- 2021/08/25 08:50 [entrez]
AID - 10.1002/JLB.1AB0821-013RR [doi]
PST - ppublish
SO  - J Leukoc Biol. 2022 Apr;111(4):793-803. doi: 10.1002/JLB.1AB0821-013RR. Epub 2021 
      Aug 25.