Epidermal Damage Induces Th1 Polarization and Defines the Site of Inflammation in Murine Epidermolysis Bullosa Acquisita
Autor: | Sebastian Klein, Markus Niebuhr, Ralf Ludwig, Katja Bieber, Jürgen Westermann, David Banczyk, Sebastian Maass, Mareike Becker, Kathrin Kalies, Detlef Zillikens |
---|---|
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Epidermolysis bullosa acquisita Collagen Type VII Ovalbumin Inflammation Dermatology Epidermolysis Bullosa Acquisita Biochemistry Proinflammatory cytokine Interferon-gamma Mice 03 medical and health sciences 0302 clinical medicine Antigen Cell Movement medicine Animals Humans Molecular Biology Autoantibodies Dermoepidermal junction Wound Healing integumentary system business.industry Autoantibody Cell Biology Th1 Cells medicine.disease Recombinant Proteins Disease Models Animal 030104 developmental biology 030220 oncology & carcinogenesis Immunology Female Bullous pemphigoid Epidermis medicine.symptom business Wound healing |
Zdroj: | Journal of Investigative Dermatology. 140:1713-1722.e9 |
ISSN: | 0022-202X |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |