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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / administration & dosage
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Antigen-Antibody Complex / chemistry
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Antigen-Antibody Complex / metabolism
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Autoantibodies / biosynthesis*
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Cell Communication / immunology
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Collagen Type VII / genetics
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Collagen Type VII / immunology
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Cricetulus
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Disease Models, Animal
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Epidermolysis Bullosa Acquisita / chemically induced
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Epidermolysis Bullosa Acquisita / immunology*
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Epidermolysis Bullosa Acquisita / pathology
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Gene Expression
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Humans
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Immunoglobulin G / biosynthesis
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Lymph Nodes / immunology
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Lymph Nodes / pathology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Nude
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Natural Killer T-Cells / immunology*
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Natural Killer T-Cells / pathology
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Neutrophils / immunology*
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Neutrophils / pathology
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Rabbits
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Receptors, Antigen, T-Cell, gamma-delta / genetics
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Receptors, Antigen, T-Cell, gamma-delta / immunology
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Signal Transduction
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Skin / immunology*
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Skin / pathology
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Spleen / immunology
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Spleen / pathology
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T-Lymphocytes / immunology*
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T-Lymphocytes / pathology
Substances
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Antibodies, Monoclonal
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Antigen-Antibody Complex
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Autoantibodies
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Col7a1 protein, mouse
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Collagen Type VII
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Immunoglobulin G
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Receptors, Antigen, T-Cell, gamma-delta