Epidermal Damage Induces Th1 Polarization and Defines the Site of Inflammation in Murine Epidermolysis Bullosa Acquisita

Markus Niebuhr, Katja Bieber, David Banczyk, Sebastian Maass, Sebastian Klein, Mareike Becker, Ralf Ludwig, Detlef Zillikens, Jürgen Westermann, Kathrin Kalies

Abstract

Epidermolysis bullosa acquisita is an autoimmune skin disease characterized by subepidermal blisters. The pathogenesis is mediated by deposits of autoantibodies directed against type VII collagen in the skin, but the sequence of events regulating the localization of skin blisters is not fully understood. In this study, using the immunization-induced mouse model of epidermolysis bullosa acquisita, we demonstrate that epidermal disruption induces not only an infiltration of CD4+ T cells but also a T helper type 1 phenotype as it has been described for delayed-type hypersensitivity reactions. This T helper type 1 reaction was not found when different antigens were applied. Deep T-cell receptor β profiling revealed shifts in the V/J gene usage only in epidermolysis bullosa acquisita, suggesting an infiltration of autoantigen-specific T cells. To target these autoantigen-specific T cells, we established an approach with which skin inflammation could be prevented without impairing the functionality of autoantibodies. We conclude that T-cell involvement in skin blistering diseases such as epidermolysis bullosa acquisita relates not only to T-cell help for B cells that produce pathogenic autoantibodies but also to autoreactive T helper type 1 effector cells that migrate into injured skin sites, exacerbate inflammation through production of inflammatory cytokines such as IFNγ, and prevent wound healing.

Original languageEnglish
JournalJournal of Investigative Dermatology
Volume140
Issue number9
Pages (from-to)1713-1722.e9
ISSN0022-202X
DOIs
Publication statusPublished - 01.09.2020

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)
  • Centers: Center for Research on Inflammation of the Skin (CRIS)

DFG Research Classification Scheme

  • 204-05 Immunology
  • 205-19 Dermatology

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