T cells mediate autoantibody-induced cutaneous inflammation and blistering in epidermolysis bullosa acquisita

Sci Rep. 2016 Dec 5:6:38357. doi: 10.1038/srep38357.

Abstract

T cells are key players in autoimmune diseases by supporting the production of autoantibodies. However, their contribution to the effector phase of antibody-mediated autoimmune dermatoses, i.e., tissue injury and inflammation of the skin, has not been investigated. In this paper, we demonstrate that T cells amplify the development of autoantibody-induced tissue injury in a prototypical, organ-specific autoimmune disease, namely epidermolysis bullosa acquisita (EBA) - characterized and caused by autoantibodies targeting type VII collagen. Specifically, we show that immune complex (IC)-induced inflammation depends on the presence of T cells - a process facilitated by T cell receptor (TCR)γδ and NKT cells. Because tissue damage in IC-induced inflammation is neutrophil-dependent, we further analyze the interplay between T cells and neutrophils in an experimental model of EBA. We demonstrate that T cells not only enhance neutrophil recruitment into the site of inflammation but also interact with neutrophils in lymphatic organs. Collectively, this study shows that T cells amplify the effector phase of antibody-induced tissue inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antigen-Antibody Complex / chemistry
  • Antigen-Antibody Complex / metabolism
  • Autoantibodies / biosynthesis*
  • Cell Communication / immunology
  • Collagen Type VII / genetics
  • Collagen Type VII / immunology
  • Cricetulus
  • Disease Models, Animal
  • Epidermolysis Bullosa Acquisita / chemically induced
  • Epidermolysis Bullosa Acquisita / immunology*
  • Epidermolysis Bullosa Acquisita / pathology
  • Gene Expression
  • Humans
  • Immunoglobulin G / biosynthesis
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Nude
  • Natural Killer T-Cells / immunology*
  • Natural Killer T-Cells / pathology
  • Neutrophils / immunology*
  • Neutrophils / pathology
  • Rabbits
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Signal Transduction
  • Skin / immunology*
  • Skin / pathology
  • Spleen / immunology
  • Spleen / pathology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology

Substances

  • Antibodies, Monoclonal
  • Antigen-Antibody Complex
  • Autoantibodies
  • Col7a1 protein, mouse
  • Collagen Type VII
  • Immunoglobulin G
  • Receptors, Antigen, T-Cell, gamma-delta