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

Cristina Martin-Granados (Lead / Corresponding author), Alan R. Prescott, Samantha Le Sommer, Izabela P. Klaska, Tian Yu, Elizabeth Muckersie, Claudiu V. Giuraniuc, Louise Grant, Mirela Delibegovic, John V. Forrester

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 by migrating from the tissues to the T cell area of the secondary lymphoid tissues. Here,wedemonstrate thatmyeloid cell-specific genetic deletion of PTP1B(LysM PTP1B) leads to defects in lipopolysaccharide-driven bone marrow-derivedDC(BMDC) activation associated with increased levels of phosphorylated Stat3.Weshowthatmyeloid cell-specific PTP1Bdeletion also causes decreased migratory capacity of epidermal DC, aswell 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 localization to podosome puncta. In co-culture with T cells, LysM PTP1B BMDC establish fewer and shorter contacts than control BMDC. Finally, LysMPTP1BBMDCfail to present antigen to T cells as efficiently as controlBMDC. 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

Fingerprint

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

Keywords

  • Adaptive immune response
  • Dendritic cell maturation
  • Podosomes
  • Protein tyrosine phosphatase 1B
  • T cell activation

Cite this

Martin-Granados, C., Prescott, A. R., Le Sommer, S., Klaska, I. P., Yu, T., Muckersie, E., ... Forrester, J. V. (2015). A key role for PTP1B in dendritic cell maturation, migration, and T cell activation. Journal of Molecular Cell Biology, 7(6), 517-528. https://doi.org/10.1093/jmcb/mjv032
Martin-Granados, Cristina ; Prescott, Alan R. ; Le Sommer, Samantha ; Klaska, Izabela P. ; Yu, Tian ; Muckersie, Elizabeth ; Giuraniuc, Claudiu V. ; 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.
@article{fd938d06806040e2bf7c708cef5d8455,
title = "A key role for PTP1B in dendritic cell maturation, migration, and T cell activation",
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 by migrating from the tissues to the T cell area of the secondary lymphoid tissues. Here,wedemonstrate thatmyeloid cell-specific genetic deletion of PTP1B(LysM PTP1B) leads to defects in lipopolysaccharide-driven bone marrow-derivedDC(BMDC) activation associated with increased levels of phosphorylated Stat3.Weshowthatmyeloid cell-specific PTP1Bdeletion also causes decreased migratory capacity of epidermal DC, aswell 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 localization to podosome puncta. In co-culture with T cells, LysM PTP1B BMDC establish fewer and shorter contacts than control BMDC. Finally, LysMPTP1BBMDCfail to present antigen to T cells as efficiently as controlBMDC. 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.",
keywords = "Adaptive immune response, Dendritic cell maturation, Podosomes, Protein tyrosine phosphatase 1B, T cell activation",
author = "Cristina Martin-Granados and Prescott, {Alan R.} and {Le Sommer}, Samantha and Klaska, {Izabela P.} and Tian Yu and Elizabeth Muckersie and Giuraniuc, {Claudiu V.} and Louise Grant and Mirela Delibegovic and Forrester, {John V.}",
year = "2015",
month = "12",
doi = "10.1093/jmcb/mjv032",
language = "English",
volume = "7",
pages = "517--528",
journal = "Journal of Molecular Cell Biology",
issn = "1674-2788",
publisher = "Oxford University Press",
number = "6",

}

Martin-Granados, C, Prescott, AR, Le Sommer, S, Klaska, IP, Yu, T, Muckersie, E, Giuraniuc, CV, Grant, L, Delibegovic, M & Forrester, JV 2015, 'A key role for PTP1B in dendritic cell maturation, migration, and T cell activation', Journal of Molecular Cell Biology, vol. 7, no. 6, pp. 517-528. https://doi.org/10.1093/jmcb/mjv032

A key role for PTP1B in dendritic cell maturation, migration, and T cell activation. / Martin-Granados, Cristina (Lead / Corresponding author); Prescott, Alan R.; Le Sommer, Samantha; Klaska, Izabela P.; Yu, Tian; Muckersie, Elizabeth; Giuraniuc, Claudiu V.; 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

TY - JOUR

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 P.

AU - Yu, Tian

AU - Muckersie, Elizabeth

AU - Giuraniuc, Claudiu V.

AU - Grant, Louise

AU - Delibegovic, Mirela

AU - Forrester, John V.

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 by migrating from the tissues to the T cell area of the secondary lymphoid tissues. Here,wedemonstrate thatmyeloid cell-specific genetic deletion of PTP1B(LysM PTP1B) leads to defects in lipopolysaccharide-driven bone marrow-derivedDC(BMDC) activation associated with increased levels of phosphorylated Stat3.Weshowthatmyeloid cell-specific PTP1Bdeletion also causes decreased migratory capacity of epidermal DC, aswell 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 localization to podosome puncta. In co-culture with T cells, LysM PTP1B BMDC establish fewer and shorter contacts than control BMDC. Finally, LysMPTP1BBMDCfail to present antigen to T cells as efficiently as controlBMDC. 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 by migrating from the tissues to the T cell area of the secondary lymphoid tissues. Here,wedemonstrate thatmyeloid cell-specific genetic deletion of PTP1B(LysM PTP1B) leads to defects in lipopolysaccharide-driven bone marrow-derivedDC(BMDC) activation associated with increased levels of phosphorylated Stat3.Weshowthatmyeloid cell-specific PTP1Bdeletion also causes decreased migratory capacity of epidermal DC, aswell 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 localization to podosome puncta. In co-culture with T cells, LysM PTP1B BMDC establish fewer and shorter contacts than control BMDC. Finally, LysMPTP1BBMDCfail to present antigen to T cells as efficiently as controlBMDC. 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 - Adaptive immune response

KW - Dendritic cell maturation

KW - Podosomes

KW - Protein tyrosine phosphatase 1B

KW - T cell activation

UR - http://www.scopus.com/inward/record.url?scp=84975735331&partnerID=8YFLogxK

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 -