γδ T cell-derived IL-17A aggravates experimental epidermolysis bullosa acquisita in response to IL-1β
- 1Research Center Borstel
Abstract
Epidermolysis bullosa acquisita (EBA) is a mucocutaneous autoimmune blistering disorder mediated by autoantibodies against type VII collagen and subsequent splitting of the dermal-epidermal junction. Interleukin (IL)-17A promotes the production of chemokines and cytokines involved in neutrophil recruitment and activation, suggesting that IL-17A may contribute to EBA pathogenesis. We aimed to clarify the role of IL-17A in experimental EBA. Using an antibody transfer-induced EBA mouse model, we demonstrate that IL-17A promotes disease development, as pharmacological blockade of IL-17A with a neutralizing antibody ameliorated skin lesions. Gamma-delta ({gamma}{delta}) T cells were identified as the predominant cellular source of IL-17A, supported by the attenuated disease phenotype observed in {gamma}{delta}TCR-deficient mice. In addition, CD4+ T cells and neutrophils contributed to IL-17A production in experimental EBA. Mechanistically, IL-1-beta, rather than IL-23, was identified as a critical mediator of IL-17A production by {gamma}{delta} T cells in vitro, consistent with our in vivo findings. Whereas EBA severity was not reduced in IL-23p19-deficient mice, disease was markedly attenuated in IL-1R-deficient animals. Together, our study provides the first evidence that {gamma}{delta} T cell-derived IL-17A plays a pivotal role in experimental EBA and identifies a previously unrecognized IL-1{beta}/{gamma}{delta} T cell/IL-17A axis that expands current understanding of EBA immunopathogenesis.
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BibTeX
@misc{deng2026γδ,
title = {{γδ T cell-derived IL-17A aggravates experimental epidermolysis bullosa acquisita in response to IL-1β}},
author = {F. Deng and S. Jukic and M. Wannick and A. Holscher and I. Prinz and R. J. Ludwig and E. Schmidt and X. Yu and F. Petersen and C. Holscher},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.04.763966},
url = {https://www.biorxiv.org/content/10.64898/2026.11.04.763966v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - γδ T cell-derived IL-17A aggravates experimental epidermolysis bullosa acquisita in response to IL-1β
AU - F. Deng
AU - S. Jukic
AU - M. Wannick
AU - A. Holscher
AU - I. Prinz
AU - R. J. Ludwig
AU - E. Schmidt
AU - X. Yu
AU - F. Petersen
AU - C. Holscher
PY - 2026
DA - 2026/11/04
PB - bioRxiv
DO - 10.64898/2026.11.04.763966
UR - https://www.biorxiv.org/content/10.64898/2026.11.04.763966v1
AB - Epidermolysis bullosa acquisita (EBA) is a mucocutaneous autoimmune blistering disorder mediated by autoantibodies against type VII collagen and subsequent splitting of the dermal-epidermal junction. Interleukin (IL)-17A promotes the production of chemokines and cytokines involved in neutrophil recruitment and activation, suggesting that IL-17A may contribute to EBA pathogenesis. We aimed to clarify the role of IL-17A in experimental EBA. Using an antibody transfer-induced EBA mouse model, we demonstrate that IL-17A promotes disease development, as pharmacological blockade of IL-17A with a neutralizing antibody ameliorated skin lesions. Gamma-delta ({gamma}{delta}) T cells were identified as the predominant cellular source of IL-17A, supported by the attenuated disease phenotype observed in {gamma}{delta}TCR-deficient mice. In addition, CD4+ T cells and neutrophils contributed to IL-17A production in experimental EBA. Mechanistically, IL-1-beta, rather than IL-23, was identified as a critical mediator of IL-17A production by {gamma}{delta} T cells in vitro, consistent with our in vivo findings. Whereas EBA severity was not reduced in IL-23p19-deficient mice, disease was markedly attenuated in IL-1R-deficient animals. Together, our study provides the first evidence that {gamma}{delta} T cell-derived IL-17A plays a pivotal role in experimental EBA and identifies a previously unrecognized IL-1{beta}/{gamma}{delta} T cell/IL-17A axis that expands current understanding of EBA immunopathogenesis.
ER -