Expression of Plet1 controls interstitial migration of murine small intestinal dendritic cells

Julien J. Karrich, Mónica Romera-Hernández, Natalie Papazian, Sharon Veenbergen, Ferry Cornelissen, Patricia Aparicio-Domingo, Frances H. Stenhouse, C. Diana Peddie, Remco M. Hoogenboezem, Chelsea W.J. den Hollander, Terri Gaskell, Tanya Medley, Louis Boon, C. Clare Blackburn, David R. Withers, Janneke N. Samsom, Tom Cupedo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Under homeostatic conditions, dendritic cells (DCs) continuously patrol the intestinal lamina propria. Upon antigen encounter, DCs initiate C-C motif chemokine receptor 7 (CCR7) expression and migrate into lymph nodes to direct T cell activation and differentiation. The mechanistic underpinnings of DC migration from the tissues to lymph nodes have been largely elucidated, contributing greatly to our understanding of DC functionality and intestinal immunity. In contrast, the molecular mechanisms allowing DCs to efficiently migrate through the complex extracellular matrix of the intestinal lamina propria prior to antigen encounter are still incompletely understood. Here we show that small intestinal murine CD11b + CD103 + DCs express Placenta-expressed transcript 1 (Plet1), a glycophoshatidylinositol (GPI)-anchored surface protein involved in migration of keratinocytes during wound healing. In the absence of Plet1, CD11b + CD103 + DCs display aberrant migratory behavior, and accumulate in the small intestine, independent of CCR7 responsiveness. RNA-sequencing indicated involvement of Plet1 in extracellular matrix-interactiveness, and subsequent in-vitro migration assays revealed that Plet1 augments the ability of DCs to migrate through extracellular matrix containing environments. In conclusion, our findings reveal that expression of Plet1 facilitates homeostatic interstitial migration of small intestinal DCs.

Original languageEnglish
Pages (from-to)290-301
Number of pages12
JournalEuropean Journal of Immunology
Volume49
Issue number2
Early online date7 Dec 2018
DOIs
Publication statusPublished - 1 Feb 2019

Keywords

  • CD103
  • Intestinal dendritic cells
  • Migration
  • Plet1
  • Wound healing

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