The CD100 receptor interacts with its plexin B2 ligand to regulate epidermal γδ T cell function

Immunity. 2012 Aug 24;37(2):314-25. doi: 10.1016/j.immuni.2012.05.026. Epub 2012 Aug 16.

Abstract

γδ T cells respond rapidly to keratinocyte damage, providing essential contributions to the skin wound healing process. The molecular interactions regulating their response are unknown. Here, we identify a role for interaction of plexin B2 with the CD100 receptor in epithelial repair. In vitro blocking of plexin B2 or CD100 inhibited γδ T cell activation. Furthermore, CD100 deficiency in vivo resulted in delayed repair of cutaneous wounds due to a disrupted γδ T cell response to keratinocyte damage. Ligation of CD100 in γδ T cells induced cellular rounding via signals through ERK kinase and cofilin. Defects in this rounding process were evident in the absence of CD100-mediated signals, thereby providing a mechanistic explanation for the defective wound healing in CD100-deficient animals. The discovery of immune functions for plexin B2 and CD100 provides insight into the complex cell-cell interactions between epithelial resident γδ T cells and the neighboring cells they support.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Depolymerizing Factors / metabolism
  • Animals
  • Antigens, CD / immunology*
  • Antigens, CD / metabolism
  • CHO Cells
  • Cell Communication / immunology
  • Cell Shape
  • Cricetinae
  • Epidermis / immunology
  • Epidermis / injuries
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • HEK293 Cells
  • Humans
  • Keratinocytes / immunology
  • Keratinocytes / metabolism
  • Langerhans Cells / immunology*
  • Langerhans Cells / metabolism
  • Lymphocyte Activation / immunology
  • Mass Spectrometry
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Tissue Proteins / immunology*
  • Nerve Tissue Proteins / metabolism
  • Phosphorylation
  • Protein Binding / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • Semaphorins / immunology*
  • Semaphorins / metabolism
  • Sequence Analysis, Protein
  • Surface Plasmon Resonance
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Wound Healing / immunology

Substances

  • Actin Depolymerizing Factors
  • Antigens, CD
  • CD100 antigen
  • Nerve Tissue Proteins
  • Plxnb2 protein, mouse
  • Receptors, Antigen, T-Cell, gamma-delta
  • Semaphorins
  • Extracellular Signal-Regulated MAP Kinases