Lesional activation of T c 17 cells in Behçet disease and psoriasis supports HLA class I-mediated autoimmune responses

• Published in: British journal of dermatology (1951) Vol. 185; no. 6; pp. 1209 - 1220
• Main Authors: Vural, S, Kerl, K, Ertop Doğan, P, Vollmer, S, Puchta, U, He, M, Arakawa, Y, Heper, A O, Karal-Öktem, A, Hartmann, D, Boyvat, A, Prinz, J C, Arakawa, A
• Format: Journal Article
• Language: English
• Published: England 01-12-2021
• Subjects: Aminopeptidases - metabolism; Autoimmunity; Behcet Syndrome - pathology; CD8-Positive T-Lymphocytes; Extracellular Traps; Humans; Minor Histocompatibility Antigens - metabolism; Psoriasis
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/bjd.20643

Behçet disease (BD) presents with lymphocytic and neutrophilic vasculitis of unknown aetiology. HLA-B*51, the endoplasmic reticulum aminopeptidase 1 (ERAP1), and interleukin 23 receptor (IL23R)/IL12R are genetic risk factors. IL-23 regulates IL-17A, which controls the recruitment and activation of neutrophils.
To determine pathological changes in BD skin lesions related to the complex genetic predisposition.
We characterized the expression of IL-17A and IL-23A in various cell types by immunohistological double staining of sections from papulopustular skin lesions of acute attacks of BD and psoriasis vulgaris lesions, another HLA-class I-associated T-cell-mediated autoimmune disease in which excessive T-cell-derived IL-17A production promotes neutrophil activation.
We found that in BD lesions, as in psoriasis, actively expanding CD8
T cells were the predominant source of IL-17A. IL-17A
CD8
T (T
17) cells outnumbered infiltrating IL-17A
CD4
T cells. Unlike the epidermal localization of CD8
T cells in psoriasis, T
17 cells in BD lesions mainly infiltrated the perivascular tissue and the blood vessel walls of dermis and subcutaneous tissue. They co-localised with a marked IL-23A expression by CD11c
dendritic cells and CD68
macrophages. IL-17A expression was associated with extensive recruitment of neutrophils around blood vessels that formed neutrophil extracellular traps (NETs).
In BD, the genetic predisposition may mediate antigen-specific activation and differentiation of a T
17 response, possibly targeting endothelial (auto)antigens. Neutrophils recruited by IL-17A in this process may enhance tissue damage by extensive NET formation (NETosis). Thus, the IL-23/IL-17 axis presumably controls neutrophilic inflammation in BD vasculitis in the context of a predominant antigen-specific CD8
T-cell response.