Differential Requirements of TCR Signaling in Homeostatic Maintenance and Function of Dendritic Epidermal T Cells

J Immunol. 2015 Nov 1;195(9):4282-91. doi: 10.4049/jimmunol.1501220. Epub 2015 Sep 25.

Abstract

Dendritic epidermal T cells (DETCs) are generated exclusively in the fetal thymus and maintained in the skin epithelium throughout postnatal life of the mouse. DETCs have restricted antigenic specificity as a result of their exclusive usage of a canonical TCR. Although the importance of the TCR in DETC development has been well established, the exact role of TCR signaling in DETC homeostasis and function remains incompletely defined. In this study, we investigated TCR signaling in fully matured DETCs by lineage-restricted deletion of the Lat gene, an essential signaling molecule downstream of the TCR. We found that Lat deletion impaired TCR-dependent cytokine gene activation and the ability of DETCs to undergo proliferative expansion. However, linker for activation of T cells-deficient DETCs were able to maintain long-term population homeostasis, although with a reduced proliferation rate. Mice with Lat deletion in DETCs exhibited delayed wound healing accompanied by impaired clonal expansion within the wound area. Our study revealed differential requirements for TCR signaling in homeostatic maintenance of DETCs and in their effector function during wound healing.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / immunology
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Flow Cytometry
  • Homeostasis / genetics
  • Homeostasis / immunology*
  • Langerhans Cells / immunology*
  • Langerhans Cells / metabolism
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism
  • Mice, Knockout
  • Mice, Transgenic
  • Microscopy, Confocal
  • Phosphoproteins / genetics
  • Phosphoproteins / immunology
  • Phosphoproteins / metabolism
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Wound Healing / genetics
  • Wound Healing / immunology

Substances

  • Adaptor Proteins, Signal Transducing
  • Lat protein, mouse
  • Luminescent Proteins
  • Membrane Proteins
  • Phosphoproteins
  • Receptors, Antigen, T-Cell