A key role for PTP1B in dendritic cell maturation, migration and T cell activation

Cristina Martin-Granados, Alan R. Prescott, Samantha Le Sommer, Izabela Klaska, Tian Yu, Elizabeth Muckersie, Vasile Claudiu Giuraniuc, Louise Grant, Mirela Delibegovic, John V Forrester

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Abstract

Dendritic cells (DC) are the major antigen-presenting cells bridging innate and adaptive immunity, a function they perform by converting quiescent DC to active, mature DC with the capacity to activate naïve T cells. They do this they do by migrating from the tissues to the T cell area of the secondary lymphoid tissues. Here, we demonstrate that myeloid-cell specificmyeloid cell-specific genetic deletion of PTP1B (LysM PTP1B) leads to defects in lipopolysaccharide-driven bone marrow-derived DC (BMDC) activation associated with increased levels of phosphorylated Stat3. We show that myeloid-cell myeloid cell-specificPTP1B deletion also causes decreased migratory capacity of epidermal DC, as well as reduced CCR7 expression and chemotaxis to CCL19 by BMDC. PTP1B deficiency in BMDC also impairs their migration in vivo. Further, immature LysM PTP1B BMDC display fewer podosomes, increased levels of phosphorylated Src at tyrosine 527, and loss of Src localisation to podosome puncta. In co-culture with T cells, LysM PTP1B BMDC establish fewer and shorter contacts than control BMDC. Finally, LysM PTP1B BMDC fail to present antigen to T cells as efficiently as control BMDC. These data provide first evidence for a key regulatory role for PTP1B in mediating a central DC function of initiating adaptive immune responses in response to innate immune cell activation.
Original languageEnglish
Pages (from-to)517-528
Number of pages12
JournalJournal of Molecular Cell Biology
Volume7
Issue number6
Early online date10 Jun 2015
DOIs
Publication statusPublished - Dec 2015

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Dendritic Cells
Cell Movement
Bone Marrow
T-Lymphocytes
Myeloid Cells
Adaptive Immunity
Innate Immunity
Langerhans Cells
Lymphoid Tissue
Antigen-Presenting Cells
Chemotaxis
Coculture Techniques
Tyrosine
Lipopolysaccharides
Antigens

Keywords

  • dendritic cell maturation
  • podosomes
  • T cell activation
  • adaptive immune response
  • protein tyrosine phosphatase 1B

Cite this

A key role for PTP1B in dendritic cell maturation, migration and T cell activation. / Martin-Granados, Cristina; Prescott, Alan R. ; Le Sommer, Samantha; Klaska, Izabela; Yu, Tian; Muckersie, Elizabeth; Giuraniuc, Vasile Claudiu; Grant, Louise; Delibegovic, Mirela; Forrester, John V.

In: Journal of Molecular Cell Biology, Vol. 7, No. 6, 12.2015, p. 517-528.

Research output: Contribution to journalArticle

Martin-Granados, Cristina ; Prescott, Alan R. ; Le Sommer, Samantha ; Klaska, Izabela ; Yu, Tian ; Muckersie, Elizabeth ; Giuraniuc, Vasile Claudiu ; Grant, Louise ; Delibegovic, Mirela ; Forrester, John V. / A key role for PTP1B in dendritic cell maturation, migration and T cell activation. In: Journal of Molecular Cell Biology. 2015 ; Vol. 7, No. 6. pp. 517-528.
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abstract = "Dendritic cells (DC) are the major antigen-presenting cells bridging innate and adaptive immunity, a function they perform by converting quiescent DC to active, mature DC with the capacity to activate na{\"i}ve T cells. They do this they do by migrating from the tissues to the T cell area of the secondary lymphoid tissues. Here, we demonstrate that myeloid-cell specificmyeloid cell-specific genetic deletion of PTP1B (LysM PTP1B) leads to defects in lipopolysaccharide-driven bone marrow-derived DC (BMDC) activation associated with increased levels of phosphorylated Stat3. We show that myeloid-cell myeloid cell-specificPTP1B deletion also causes decreased migratory capacity of epidermal DC, as well as reduced CCR7 expression and chemotaxis to CCL19 by BMDC. PTP1B deficiency in BMDC also impairs their migration in vivo. Further, immature LysM PTP1B BMDC display fewer podosomes, increased levels of phosphorylated Src at tyrosine 527, and loss of Src localisation to podosome puncta. In co-culture with T cells, LysM PTP1B BMDC establish fewer and shorter contacts than control BMDC. Finally, LysM PTP1B BMDC fail to present antigen to T cells as efficiently as control BMDC. These data provide first evidence for a key regulatory role for PTP1B in mediating a central DC function of initiating adaptive immune responses in response to innate immune cell activation.",
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note = "Acknowledgements We thank the Iain Fraser Flow Cytometry Centre and the Medical Research Facility of the University of Aberdeen. We are grateful to Drs West, Zaru, and Davidson (University of Dundee) for the scientific discussion and technical assistance. Wethank Derek Mitchell (University of Dundee) for aiding with the quantification of focal contacts. Funding This work was supported by Saving Sight in Grampian and the Development Trust of the UoA (both to J.V.F.). Work on this project was partly funded by project grants from British Heart Foundation and European Foundation for the Study of Diabetes/Lilly diabetes programme grant (to M.D.).",
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T1 - A key role for PTP1B in dendritic cell maturation, migration and T cell activation

AU - Martin-Granados, Cristina

AU - Prescott, Alan R.

AU - Le Sommer, Samantha

AU - Klaska, Izabela

AU - Yu, Tian

AU - Muckersie, Elizabeth

AU - Giuraniuc, Vasile Claudiu

AU - Grant, Louise

AU - Delibegovic, Mirela

AU - Forrester, John V

N1 - Acknowledgements We thank the Iain Fraser Flow Cytometry Centre and the Medical Research Facility of the University of Aberdeen. We are grateful to Drs West, Zaru, and Davidson (University of Dundee) for the scientific discussion and technical assistance. Wethank Derek Mitchell (University of Dundee) for aiding with the quantification of focal contacts. Funding This work was supported by Saving Sight in Grampian and the Development Trust of the UoA (both to J.V.F.). Work on this project was partly funded by project grants from British Heart Foundation and European Foundation for the Study of Diabetes/Lilly diabetes programme grant (to M.D.).

PY - 2015/12

Y1 - 2015/12

N2 - Dendritic cells (DC) are the major antigen-presenting cells bridging innate and adaptive immunity, a function they perform by converting quiescent DC to active, mature DC with the capacity to activate naïve T cells. They do this they do by migrating from the tissues to the T cell area of the secondary lymphoid tissues. Here, we demonstrate that myeloid-cell specificmyeloid cell-specific genetic deletion of PTP1B (LysM PTP1B) leads to defects in lipopolysaccharide-driven bone marrow-derived DC (BMDC) activation associated with increased levels of phosphorylated Stat3. We show that myeloid-cell myeloid cell-specificPTP1B deletion also causes decreased migratory capacity of epidermal DC, as well as reduced CCR7 expression and chemotaxis to CCL19 by BMDC. PTP1B deficiency in BMDC also impairs their migration in vivo. Further, immature LysM PTP1B BMDC display fewer podosomes, increased levels of phosphorylated Src at tyrosine 527, and loss of Src localisation to podosome puncta. In co-culture with T cells, LysM PTP1B BMDC establish fewer and shorter contacts than control BMDC. Finally, LysM PTP1B BMDC fail to present antigen to T cells as efficiently as control BMDC. These data provide first evidence for a key regulatory role for PTP1B in mediating a central DC function of initiating adaptive immune responses in response to innate immune cell activation.

AB - Dendritic cells (DC) are the major antigen-presenting cells bridging innate and adaptive immunity, a function they perform by converting quiescent DC to active, mature DC with the capacity to activate naïve T cells. They do this they do by migrating from the tissues to the T cell area of the secondary lymphoid tissues. Here, we demonstrate that myeloid-cell specificmyeloid cell-specific genetic deletion of PTP1B (LysM PTP1B) leads to defects in lipopolysaccharide-driven bone marrow-derived DC (BMDC) activation associated with increased levels of phosphorylated Stat3. We show that myeloid-cell myeloid cell-specificPTP1B deletion also causes decreased migratory capacity of epidermal DC, as well as reduced CCR7 expression and chemotaxis to CCL19 by BMDC. PTP1B deficiency in BMDC also impairs their migration in vivo. Further, immature LysM PTP1B BMDC display fewer podosomes, increased levels of phosphorylated Src at tyrosine 527, and loss of Src localisation to podosome puncta. In co-culture with T cells, LysM PTP1B BMDC establish fewer and shorter contacts than control BMDC. Finally, LysM PTP1B BMDC fail to present antigen to T cells as efficiently as control BMDC. These data provide first evidence for a key regulatory role for PTP1B in mediating a central DC function of initiating adaptive immune responses in response to innate immune cell activation.

KW - dendritic cell maturation

KW - podosomes

KW - T cell activation

KW - adaptive immune response

KW - protein tyrosine phosphatase 1B

U2 - 10.1093/jmcb/mjv032

DO - 10.1093/jmcb/mjv032

M3 - Article

VL - 7

SP - 517

EP - 528

JO - Journal of Molecular Cell Biology

JF - Journal of Molecular Cell Biology

SN - 1674-2788

IS - 6

ER -