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

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12 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

Keywords

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

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    Martin-Granados, C., Prescott, A. R., Le Sommer, S., Klaska, I. P., Yu, T., Muckersie, E., Giuraniuc, C. V., Grant, L., Delibegovic, M., & 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